For knee osteoarthritis, I recommend starting with a topical NSAID gel, like diclofenac, applied directly to the knees. It provides targeted relief with very few systemic side effects. For oral options, acetaminophen (Tylenol) is a good starting point for mild pain. If your pain is moderate to severe, oral anti-inflammatories (NSAIDs) like ibuprofen or naproxen can be highly effective at reducing both pain and inflammation. However, because oral NSAIDs can affect your stomach, kidneys, and blood pressure, please consult your doctor first to determine the safest option and dosage for your specific medical history.