How to Use OTC Pain Relievers Safely: Acetaminophen vs. NSAIDs Explained

Over-the-counter (OTC) pain relievers are medications you can buy without a prescription to treat headaches, muscle aches, fever, and minor injuries. But these popular drugs aren't all the same, and should be used with care.

Woman in glasses holding a box of medication while standing among shelves at a drug store

Updated February 17, 2026

By Mithil Choksey, MD, Internal Medicine Physician, Virtua Primary Care

Headache? Sore back? Achy knees? When pain shows up uninvited, most of us reach for the medicine cabinet without a second thought. But before you take over-the-counter (OTC) pain relievers, it’s worth brushing up on how to use them safely and smartly.

Over-the-counter pain relievers are convenient because you don’t need a prescription, and they treat all sorts of pain. Not all of these medicines work the same way, however, so seek medical advice if you are using one for the first time or for a new problem.

Here’s what you need to know to feel better safely.

Types of OTC pain relievers: acetaminophen vs. NSAIDs

OTC pain relievers fall into two main categories: acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). Each works a little differently and comes with its own pros and cons.

Acetaminophen

Sold as: Tylenol

Used for: Headaches, fevers, arthritis, general aches and pains

Pros: Few side effects, and should be the first choice for older adults

Cons: Doesn’t help with inflammation, and high doses can damage your liver

NSAIDs

Sold as: Ibuprofen (Advil, Motrin), aspirin (Bayer, St. Joseph), naproxen (Aleve), diclofenac (Voltaren) gel

Used for: Fevers, muscle aches and stiffness, menstrual cramps, sprains

Pros: Tackles both pain and inflammation. Diclofenac gel, applied to the skin, is as effective as NSAIDs pills, with fewer side effects.

Cons: Can irritate your stomach, affect your kidney function, and raise your blood pressure

There are combination drugs like Excedrin, which contains aspirin, acetaminophen, and caffeine. Excedrin is often used to treat tension and migraine headaches, but, because of its multiple ingredients, can carry additional risks.

How to use OTC pain relievers safely

OTC meds can be a helpful fix for short-term issues. However, to use them safely, you should follow a few key guidelines:

Check the label. Only take the recommended dose, and don’t keep using it longer than advised.
Loop in your provider. If you’re already taking a prescription, ask if it’s safe to add an OTC medicine.
Don’t mix meds. Only take one type of OTC pain reliever at a time unless your provider says it’s safe to combine them.
Keep it short and simple. Take the lowest dose you need for the shortest time possible.

Who should avoid OTC pain relievers?

Do not use acetaminophen if you have severe liver disease or if you regularly drink alcohol.

Talk with your provider before taking NSAIDs if you have heart, liver, or kidney disease; high blood pressure; stomach ulcers; a bleeding disorder; or take blood thinners.

Older individuals should be cautious or avoid NSAIDs due to increased side effects. They are also not recommended later in pregnancy because they can increase the risk of complications.

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