ABSTRACT: BACKGROUND:Effective analgesia is essential for patient recovery after liver resection. This study aimed to evaluate the effects of the addition of preoperative intrathecal morphine to multimodal intravenous analgesia in patients undergoing liver resection. METHODS:In this single-blind randomized controlled trial, patients undergoing liver resection were randomly assigned to the patient-controlled analgesia with (ITM-IV) or without (IV) preoperative intrathecal morphine groups. All patients received acetaminophen and dexketoprofen. The primary outcome was pain severity at rest over three postoperative days, assessed using the numerical rating scale (NRS). RESULTS:The study included 36 patients (18 in each group). The mean maximum daily NRS scores over the first three postoperative days in the ITM-IV and IV groups were 1.3, 1.1, and 0.3 and 1.6, 1.1, and 0.7, respectively (p?=?0.580). No differences were observed in pain severity while coughing, with corresponding scores of 2.8, 2.1, and 1.1, respectively, in the ITM-IV group and 2.3, 2.2, and 1.5, respectively, in the IV group (p?=?0.963). Proportions of patients reporting clinically significant pain at rest and while coughing were 11.1% and 44.4%, respectively, in the ITM-IV group, and 16.7% and 44.4%, respectively, in the IV group (both p?>?0.999). Cumulative morphine doses in the ITM-IV and IV groups were 26 mg and 17 mg, respectively (p?=?0.257). Both groups also showed similar time to mobilization (p?=?0.791) and solid food intake (p?=?0.743), sedation grade (p?=?0.584), and morbidity (p?=?0.402). CONCLUSIONS:Preoperative intrathecal morphine administration provides no benefits to multimodal analgesia in patients undergoing liver resection. TRIAL REGISTRATION NUMBER:Clinicaltrial.gov Identifier: NCT03620916.