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Few studies demonstrate the safety and efficacy of postoperative pain regimens that exclude opioids altogether in patients undergoing robot-assisted radical prostatectomy (RARP). To reduce opioid use, we sought to develop an opioid-free regimen for RARP and determine perioperative outcomes before and after implementation. A retrospective, pre-post-interventional study was performed at a single institution between 8/2018 and 10/2019. An opioid-free pain regimen was developed and instituted on 3/7/2019, and all patients received preoperative counseling regarding pain expectations and management. Postoperative pain score was the primary outcome. Secondary outcomes included postoperative opioid use, length of stay, adverse events and unplanned health encounters within 30 days of discharge. Pearson's chi-squared and Student's t-tests were performed on categorical and continuous variables, respectively. Multivariable analysis was performed to determine risk factors for postoperative opioid use in the opioid-free cohort. A total of 89 patients were included for analysis; consisting of 47 (53%) pre-intervention and 42 (47%) post-intervention patients. Baseline characteristics were similar between groups. A significantly lower proportion of patients in the post-intervention group were administered opioids postoperatively (5% vs 53%, p < 0.01), despite having similar postoperative pain scores (2.69 vs 3.11, p = 0.19) and length of stay (1.0 days vs 1.2 days, p = 0.07). The post-intervention group had a significantly lower rate of opioid discharge prescriptions (14% vs 96%, p < 0.01). The rate of ED visits (12% vs 15%, p = 0.68), pain-related phone calls (17% vs 19%, p = 0.76) or adverse events (19% vs 13%, p = 0.42) were similar between groups. Among the opioid-free group, older patients were less likely to be administered postoperative opioids (OR 0.84, p = 0.046). A structured opioid-free pain regimen following RARP is non-inferior compared to traditional opioid-based standard of care. Adoption of similar regimens can help address the ongoing opioid epidemic in the United States and future work is needed to apply these principles broadly., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd. part of Springer Nature.)