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Background and Aims Transmuscular quadratus lumborum block (TQLB) is a regional anesthesia technique widely utilized in multimodal analgesia strategies for abdominal surgeries. While a few studies have inves-tigated its efficacy in multiport total laparoscopic hysterectomy (TLH), its effectiveness in single-port TLH remains uncertain. This study aimed to evaluate whether QLB reduces opioid consumption and postoperative pain in patients undergoing single-port TLH.Methods This prospective randomized, controlled, observer-blinded trial adhered to the principles outlined in the Declaration of Helsinki. Ethical approval (DIRB-00146_2–006) was obtained from the Institutional Review Board of The Catholic University of Korea. A total of 64 patients undergoing elective single-port total laparoscopic hysterectomy (TLH) were included in the trial. Participants were randomly assigned to either the transmuscular quadratus lumborum block (TQLB) group (n = 27) or the control group (n = 29). Bilateral TQLB was performed under ultrasound guidance after surgery. The primary outcome was cumulative fentanyl consumption within 24 hours postoperatively. Secondary outcomes included pain scores at predefined intervals, time to first opioid demand, the incidence of postoperative nausea and vomiting (PONV), and other complications.Results The 24-hour cumulative fentanyl consumption, which was the primary outcome, did not differ significantly between the TQLB group 470 [191.6, 648.1] mcg and the control group 342.8 [220, 651] mcg (P = 0.714). Additionally, cumulative fentanyl consumption at other time points, including 2 h, 4 h, 8 h, 12 h, 32 h, and 48 h, as well as in the PACU, also showed no significant differences between the two groups. Pain scores measured at these time points, along with the time to first bolus on demand, similarly showed no significant differences between the groups.Conclusions Bilateral TQLB did not reduce opioid consumption or pain scores in patients under-going single-port TLH. These results suggest that TQLB offers no significant benefit as part of multimodal analgesia after single port TLH.