OBJECTIVE To compare the efficacy of opioid versus nonopioid analgesic regimens after elective, soft tissue hand surgery. We hypothesized that there would be no difference in patient-perceived pain relief between these 2 groups. METHODS This prospective, randomized, double-blinded controlled trial included patients undergoing elective soft tissue hand procedures (carpal tunnel release, trigger finger release, first dorsal compartment release, or ganglion cyst excision). Patients were randomized before surgery into 2 treatment groups: acetaminophen/hydrocodone 325/5 mg (AH, opioid group) or acetaminophen/ibuprofen 500/400 mg (AIBU, nonopioid group) and followed for 2 weeks after surgery evaluating daily pain intensity scores-visual analog scale (VAS), medication pain relief (Likert pain relief score), need for rescue opioid prescription at 1 week, and days until pain-free. RESULTS Sixty patients were randomized, 30 in the AH group and 30 in the AIBU group. There was no difference in the average VAS score. There was improved pain relief in the AIBU group, but the difference did not reach significance. There was no difference in time until pain-free, with a median of 5 days in the AH group and 3 days in the AIBU group. Two patients in each group required rescue opioid medication. Side effects were significantly more common in the AH group (n = 7; 23%) than the AIBU group (n = 1; 3%), but none were severe. CONCLUSIONS We recommend surgeons consider a combination of acetaminophen and ibuprofen as a safe and effective postoperative pain regimen for soft tissue hand surgery procedures. METHODS Therapeutic I.