Fifty college athletes with acute sprains and strains from football-related activities were randomly assigned to treatment with either diflunisal or acetaminophen with codeine for seven days. Additional treatment in both groups included rest, elevation, local application of cold or heat, splinting, and physical therapy, as indicated. Both treatment groups exhibited clinically significant improvements in pain, tenderness, and swelling. The results of this study show that diflunisal, a peripherally acting nonnarcotic nonsteroidal anti-inflammatory agent with analgesic properties, was as effective as acetaminophen with codeine in relieving mild to moderate pain due to musculo-skeletal sprains and strains. The long duration of action of diflunisal permits less frequent dosing, an important consideration when prescribing medication for active young adults.