Benadryl Cream vs. Hydrocortisone Cream: Which Works Best to Soothe Itchy Skin?

Bug bites, pollen, poison ivy — whatever the cause, itchy skin (pruritus) is very unpleasant.

Itching can be caused by chemical signals the body releases, such as histamine. These chemicals play an important role in our immune system by helping protect us from foreign invaders. But there are other immune signals besides histamine that can cause itchy skin. This makes it a hard condition to treat for some people.

Below, we’ll talk about two common creams that you might use to treat itchy skin: Benadryl Itch Relief cream (diphenhydramine / zinc acetate) and hydrocortisone cream. Read on to learn six ways these anti-itch creams compare.

1. Benadryl cream and hydrocortisone cream belong to different medication classes

Benadryl cream is an antihistamine cream that contains the medication diphenhydramine. Most topical (applied to the skin) Benadryl products also contain zinc acetate as a skin protectant. Benadryl cream is available over-the-counter (OTC) and has generic versions available. 

Hydrocortisone cream is a corticosteroid medication that’s applied to the skin. Lower doses (1% or less) of hydrocortisone cream are available OTC. Higher doses, such as 2% or 2.5%, require a prescription from a healthcare professional.

2. Both products treat many itchy skin conditions

Many people take oral antihistamines to treat systemic (body-wide) allergy symptoms, such as sneezing or hives. But Benadryl cream may be preferable when you're only having mild allergic skin reactions in certain areas. Benadryl cream can be used to temporarily relieve itching caused by:

• Mosquito bites

• Sunburn

• Other minor burns

• Rashes from poison ivy, oak, or sumac

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OTC hydrocortisone cream can be used to relieve inflammation and itchy skin from many conditions. Examples include:

• Skin inflammation or rashes

• Psoriasis

• Eczema

• Bug bites

• Genital or rectal irritation

• Rashes from poison ivy, oak, or sumac

3. Benadryl cream and hydrocortisone cream work differently

Benadryl cream and diphenhydramine cream both help with itching. But they do so in different ways.

The diphenhydramine in Benadryl cream works by blocking histamine from attaching to different cells in your body. Our immune system normally releases histamine when it senses something potentially harmful or out of place. In some cases, this triggers allergy symptoms, like itchy skin. However, Benadryl cream doesn’t work for everyone. This is because other inflammation signals besides histamine can cause itching.

Hydrocortisone cream works in several ways to help itching, by comparison. The three main effects that help with itching include:

1. It prevents inflammation (swelling). Corticosteroids like hydrocortisone lessen or stop the release of chemicals in the body that cause inflammation. They also help narrow blood vessels where you apply it, cutting down on swelling.

2. It slows cell replication. This can be helpful in improving itching for people with psoriasis. This action can slow down how quickly the body makes new skin cells. And this can help lessen some psoriasis symptoms, including itching.

3. It can weaken the immune system’s response. Skin inflammation can be triggered by overactive immune cells. Hydrocortisone cream can help lower the immune response in these cells.

EXPERT PICKS: WHAT TO READ NEXT

• Not all topicals are the same: Pharmacists and physicians explain the differences between creams, lotions, and ointments. 

• Know before you apply: Here’s what you should know about topical corticosteroids (steroids). 

• Other possible causes of itchy skin: Learn about common medications that can make you feel itchy.

4. They have similar dosages

The directions for using Benadryl cream and OTC hydrocortisone cream are similar. You can apply Benadryl cream up to 3 to 4 times a day. You can also apply a thin film of OTC hydrocortisone cream 3 to 4 times daily. Both anti-itch creams should only be used as needed, unless a healthcare professional tells you otherwise.

Both Benadryl cream and OTC hydrocortisone cream can be used by adults and children ages 2 years and older. Parents with children under 2 years old should speak with their child’s pediatrician before using either cream.

Prescription-strength hydrocortisone may have different directions from the OTC version. Be sure to follow the instructions on your prescription label.

5. There is slightly more evidence that supports hydrocortisone cream for itchy skin

Studies that directly compare Benadryl cream to OTC hydrocortisone cream are lacking. But we can review what we know about the effectiveness of each anti-itch cream.

Benadryl cream

It’s unclear exactly how effective Benadryl cream is for itchy skin. A review of several studies showed mixed results. A few of these studies found that topical antihistamines were effective. But other studies did not find any benefit. Overall, the review’s authors concluded that there wasn’t much evidence supporting antihistamine creams’ effectiveness, including Benadryl cream.

Some experts also believe that Benadryl cream can make symptoms worse for mosquito bites. This is because the cream can cause allergic skin reactions for some people.

Hydrocortisone cream

There is slightly more evidence supporting hydrocortisone cream for itchy skin. One study compared a prescription version of hydrocortisone cream to placebo (a cream containing no medication) in people with eczema. People using hydrocortisone cream had greater symptom improvement than those using placebo. But keep in mind this study looked at a prescription-strength hydrocortisone cream, not the OTC version.

A review of many studies looked at topical steroids, including hydrocortisone, for relieving itching due to eczema. Overall, the studies found that topical steroids provided about a 34% improvement in itching.

Research surrounding hydrocortisone’s use for itchy skin due to common triggers, like bug bites, is lacking. But because hydrocortisone cream treats itching in multiple ways, it may be recommended by a healthcare professional for many itchy skin problems.

6. Benadryl cream and hydrocortisone cream can occasionally cause side effects

When used for short periods of time, Benadryl cream and OTC hydrocortisone cream are usually tolerated well. Side effects can still occur, though.

Benadryl cream is sometimes linked to:

• Rash

• Sunburn

• Sun sensitivity

People using hydrocortisone cream may experience:

• Burning

• Irritation

• Skin dryness or redness

• Pimples that look like acne

If you experience any bothersome side effects after using Benadryl cream or hydrocortisone cream, contact a healthcare professional for next steps.

Serious side effects of Benadryl cream and hydrocortisone cream

People shouldn’t apply Benadryl cream to itchy skin caused by issues such as chickenpox or measles. These rashes can cover large areas. Applying too much Benadryl cream can cause it to be absorbed into the blood. In rare cases, this can lead to dangerously high levels of Benadryl and can be life-threatening.

Taking other medications that also contain diphenhydramine at the same time, like oral Benadryl, raises your risk of complications. Possible symptoms of a Benadryl overdose include:

• Dry mouth

• Drowsiness

• Slowed breathing

• Low blood pressure

• Irregular heart beat

Call 911 or Poison Control at 1-800-222-1222 right away if you or someone you know are experiencing symptoms of a Benadryl overdose.

In rare cases, hydrocortisone cream can also absorb through the skin and enter the bloodstream. Children may be at higher risk than adults for serious problems. Using hydrocortisone cream for a long time or over large areas of the body can lead to potentially serious side effects, such as:

• Hormone changes

• Cushing’s syndrome

• High blood glucose (blood sugar)

• Higher risk of infection

• Topical steroid withdrawal

Let a healthcare professional know if your symptoms worsen or don’t improve while using Benadryl cream or hydrocortisone cream. These may not be the best options for your itching.

How to save on Benadryl cream and hydrocortisone cream

Benadryl cream and OTC hydrocortisone cream are available as brand-name medications. But you can also find them as lower-cost generics. GoodRx can help you save over 60% off the average retail price of the generic version of Benadryl cream and hydrocortisone cream. Generic Benadryl cream’s price at certain pharmacies is as low as $4.47 with a free GoodRx discount. Generic hydrocortisone cream’s price at certain pharmacies is as low as $15.66 with a free GoodRx discount.

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Written by:

Arnisha Carter, PharmD, BCPS

Arnisha Carter, PharmD, BCPS, is a licensed pharmacist in Florida. She’s worked in the pharmacy industry for more than 10 years and began writing for GoodRx in 2024.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Maria Robinson, MD, MBA

Maria Robinson, MD, MBA, is a board-certified dermatologist and dermatopathologist who has practiced dermatology and dermatopathology for over 10 years across private practice, academic, and telehealth settings. She is a fellow of the American Academy of Dermatology and the American Society of Dermatopathology.

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