Six hundred patients presenting to the 2 urban center emergency departments with acute musculoskeletal pain in ≥1 extremities lasting for >7 days and which the attending physician was willing to administer oral analgesics were randomized to receive either of the 5 oral analgesic combinations: (1) 400 mg ibuprofen plus 1,000 mg acetaminophen; (2) 800 mg ibuprofen plus 1,000 mg acetaminophen; (3) 30 mg codeine plus 300 mg acetaminophen; (4) 5 mg hydrocodone plus 300 mg acetaminophen; (5) 5 mg oxycodone plus 325 mg acetaminophen. The primary outcome of interest was decrease in pain from baseline using the Numeric Rating Scale (NRS) at 1 hour post-intervention. Secondary outcomes of interest included the following: decrease in pain using NRS at 2 hours follow-up from baseline, incidence of adverse events, receipt of rescue medication at 2 hours post-intervention, satisfaction with pain relief, satisfaction with time to satisfaction with pain relief, and whether they would prefer the same pain medication in the future. Results demonstrated that all outcomes were not statistically significantly different across the 5 intervention groups at any of the timepoints (p>0.05). Adverse events that were observed in all groups included drowsiness/dizziness/lightheaded, nausea/vomiting, abdominal pain/heartburn, and gas/diarrhea. Also, rash/itchiness were observed in groups 2, 3, and 4 only.