240 patients with moderate-to-severe chronic low back pain, knee osteoarthritis pain, or hip osteoarthritis pain were randomized to analgesia through either an opioid or nonopioid medication regimen. Patients were assessed over 12-month follow-up for efficacy outcomes related to pain-related function, pain severity, quality-of-life and disability, and safety outcomes related to adverse events and potential opioid misuse. Despite no significant difference in pain-related function scores over 12 months, significantly worse results for pain severity over 12-month follow-up were observed in the opioid group compared to the nonopioid group. Checklist scores for medication-related adverse events demonstrated significantly higher scores in the opioid group compared to the nonopioid group throughout follow-up.