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BackgroundEffective pain management is critical following hemorrhoidectomy due to the dense nerve distribution in the anorectal region. Although compound methylene blue and liposomal bupivacaine are both used for postoperative analgesia, their comparative efficacy and safety profiles have not been systematically evaluated. This study aimed to compare the analgesic efficacy, opioid-sparing effects, and safety of liposomal bupivacaine with compound methylene blue in patients undergoing mixed hemorrhoidectomy.MethodsThis was a single-center, prospective observational cohort study involving 150 patients undergoing elective hemorrhoidectomy for stage III-IV mixed hemorrhoids. Patients were allocated into two groups: (a) the compound methylene blue group (n = 75) and (b) the liposomal bupivacaine group (n = 75). Postoperative pain was assessed using the numerical rating scale at rest over 72 h. Primary outcomes included cumulative pain scores, time to first rescue analgesia, and total rescue opioid consumption. Secondary outcomes included patient satisfaction, recovery metrics, and adverse events.ResultsThe liposomal bupivacaine group demonstrated significantly lower cumulative pain scores over 72 h than the compound methylene blue group. Although the compound methylene blue group demonstrated marginally better pain control in the immediate postoperative period, liposomal bupivacaine provided superior and stable analgesia from 12 to 72 h. The proportion of patients who required rescue opioids was significantly lower in the liposomal bupivacaine group than in the compound methylene blue group. Patient satisfaction was significantly higher in the liposomal bupivacaine group. Furthermore, the incidence of adverse events was significantly lower in the liposomal bupivacaine group than in the compound methylene blue group.ConclusionsSingle-dose perianal infiltration of liposomal bupivacaine provides superior and more sustained postoperative analgesia than that of compound methylene blue in patients who have undergone mixed hemorrhoidectomy. Liposomal bupivacaine significantly reduces rescue opioid requirements, delays the need for supplemental analgesia, and improves patient satisfaction with a favorable safety profile.