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Study Objective: The efficacy of infiltration of liposomal bupivacaine against an active comparator, such as bupivacaine, remains debated on acute postoperative pain control. We evaluated the analgesic efficacy, patient satisfaction, and side effects of liposomal bupivacaine compared to bupivacaine during hemorrhoidectomy procedures., Design: A pre- and post-implementation quality improvement evaluation., Setting: Operating room and post-anesthesia care unit., Patients: Ninety-four consecutive adult patients with hemorrhoid surgery between October 2019 and November 2020., Interventions: A preintervention control group of 0.25% bupivacaine (50 ml, 125 mg, n = 47) and a postintervention group of liposomal bupivacaine (30 ml, 266 mg, n = 47) for perianal local anesthetic administration., Measurements: The primary endpoint was analgesic efficacy of liposomal bupivacaine compared to bupivacaine based on a reduction in the number of patients administered opioids and patient-reported pain scores in the postanesthesia care unit (PACU). Secondary endpoints included constipation, post-discharge patient-reported pain management satisfaction, and opioid prescription refill requests in telephonic interviews three days after surgery., Main Results: PACU peak pain scores were significantly higher in the bupivacaine compared to the liposomal bupivacaine group (median 3 [IQR 0-6] vs. 0 [IQR 0-4], p = 0.03), respectively with no differences in PACU discharge pain scores. There was no difference in the frequency of rescue opioid use (38.2% vs. 25.5%, p = 0.18) or the morphine milligram equivalents administered to each of those patients (median 15 [IQR 10-23] vs. 15 [IQR 15-25], p = 0.39) in the PACU comparing the bupivacaine and liposomal bupivacaine groups respectively. Secondary endpoints were similar in each group with respect to requests for opioid refills (10.6 vs. 12.8%, p = 0.75), >75% satisfied with their pain management (p = 0.94), and constipation reported on day 3 after surgery (p = 0.07)., Conclusions: Liposomal bupivacaine compared to a bupivacaine perianal block reduces early PACU pain scores without affecting opioid refill requests, has a similarly low incidence of complications, and high satisfaction in both groups., (Copyright © 2022 Elsevier Inc. All rights reserved.)