This study will determine if there is a difference between commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (a pain-reliever that does not prevent inflammation) for treating knee pain in osteoarthritis (OA). The two main results we will look at are disease progression according to x-rays and disability over 3.5 years. Study participants with moderate knee OA and knee pain will continue taking their NSAID or stop taking their NSAID and start taking acetaminophen. Every 6 months we will send the participants questionnaires that ask about pain, medication use, and disability. We will take x-rays of the knees at the start of the study and again at the end of the study.