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Opiate-based regimens have been used as a foundation of postoperative analgesia in orthopedic surgery for decades, and the vast majority of orthopedic patients in the United States receive postoperative opioid prescriptions. Both the safety and efficacy of opioid use in orthopedic patients have been questioned because of mounting evidence that postoperative opioid use can be detrimental to outcomes and patient satisfaction. The purpose of this study is to compare a new, opioid-free pain management pathway with a traditional opioid-containing, multimodal pathway in patients undergoing shoulder arthroplasty.This is a single-center randomized clinical trial in which 67 patients who underwent shoulder arthroplasty were allocated into 2 treatment arms: either a completely opioid-free, multimodal perioperative pain management pathway (OF), or a traditional opioid-containing perioperative pain management pathway (OC). Pain was measured on a numeric rating scale from 0 to 10 at 6-, 12-, 24-hour, 2-week, and 6-week time points. Deviations from the OF pathway, morphine milligram equivalents, readmissions, and opioid-related side effects were analyzed.Pain levels were significantly lower in the OF group at 12 hours, 24 hours, and 2 weeks. At 12 hours, the median pain rating was 0 compared with a median pain rating of 3 in the OC group (P = .003). At 24 hours, the OF group reported a median pain rating of 1 and the OC group reported a median pain rating of 4 (P .001). The median pain rating at the 2-week time point in the OF group was 2 compared with 4 in the OC group (P = .006). Median pain ratings were similar between the OF group and the OC group at the 6-week time point. The median pain rating in the OF group at 6 weeks was 1, compared with 1.5 in the OC group. Of the 35 patients in the OF pathway, 1 required a rescue opioid medication for left cervical radiculopathy that ultimately necessitated cervical spine fusion after recovery from right shoulder arthroplasty, and 1 was noted to have taken an opioid medication, diverted from a prior prescription, at the 2-week visit. The morphine milliequivalents received in the OF group was 20 compared with 4936.25 in the OC group. There were no readmissions in the OF pathway, and no differences between the groups with regard to constipation, falls, or delirium.A multimodal, opioid-free perioperative pain management pathway is safe and effective in patients undergoing total shoulder arthroplasty and offers superior pain relief to that of a traditional opioid-containing pain management pathway at 12 hours, 24 hours, and 2 weeks postoperatively.