ObjectiveTo explore the analgesic effect of local infiltration anesthesia with liposome bupivacaine (LB) after Milligan-Morgan hemorrhoidectomy through a multicenter, double-blind, randomized controlled study. MethodsA prospective study was conducted on 240 patients with mixed hemorrhoids admitted to the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou Hospital for Largeintestinal and Anal Diseases, and Puyang People’s Hospital between December 2023 and June 2024. Patients were randomly divided into an observation group (receiving liposome bupivacaine injection) and a control group (receiving methylene blue injection) using a random number table. Postoperative outcomes including pain (VAS) scores, insomnia scores, postoperative edema, urination, time to first defecation, pain during first defecation, perianal sensory recovery time, hospital stay, need for additional analgesic medication, and postoperative complications were compared between the two groups. ResultsAmong 240 patients, 238 completed the study and were included in the analysis, with 119 patients in the observation group and 119 in the control group.① There were no statistically significant differences in baseline characteristics between the two groups (P>0.05).② Postoperative anal pain scores at 6 h, 12 h, 24 h, 48 h, 72 h, and 5 days were lower in the observation group than in the control group (P<0.05).③ Postoperative insomnia scores on days 1, 2, 3, and 5 were lower in the observation group compared with the control group (P<0.05).④ Postoperative edema scores on days 3, 5, and 7 were lower in the observation group than in the control group (P<0.001).⑤ The observation group showed superior outcomes compared to the control group in the following parameters: postoperative 24-hour urination score [0 points vs. 0 points, Z=–2.528, P=0.011]、time to first defecation [2 days vs. 2 days, Z=–2.638, P=0.008]、pain score at first defecation [3 points vs. 5 points, Z=–2.528, P<0.001]、time to recovery of perianal sensation [2 days vs. 1 day, Z=–4.977, P<0.001]、hospital stay duration [6 days vs. 11 days, Z=–12.170, P<0.001]、supplemental analgesic medication need at 7 days postoperation [20.1% vs. 80.7%, χ2 = 87.132, P<0.001]. No statistically significant differences were observed between the two groups in the incidence of complications such as:postoperative nausea [6.7% vs. 8.4%, χ2 = 0.240, P=0.624]、vomiting [5.0% vs. 7.6%, χ2 = 0.640, P=0.424]、dizziness [1.7% vs. 4.2%, χ2=1.325, P=0.250]. ConclusionsLocal infiltration anesthesia with LB after Milligan-Morgan hemorrhoidectomy significantly reduces postoperative pain, insomnia, and edema, shortens hospital stays, and accelerates postoperative recovery. LB demonstrates broad clinical application potential.