Background & Objectives: Radical cystectomy (RC) is usually performed under general anesthesia, with the management of postoperative pain being a big challenge. Various approaches have been tried, including epidural analgesia, or regional nerve blocks in addition to the intravenous patient-controlled analgesia (IV-PCA). We compared the efficacy and safety of bilateral single-injection erector spinae plane block (ESPB) with IV-PCA administered morphine to manage postoperative pain following RC. Methodology: This prospective randomized controlled clinical study was performed on 60 participants ranging in age from 21 to 65 years, both sexes, BMI 20-40 kg/m2, ASA physical status II-III, planned for elective RC. Participants were randomized into two equal groups. Group ESPB received ultrasound-guided single shot ESPB at T10 with 20 mL bupivacaine 0.25% bilaterally; IV morphine 3 mg bolus was used as rescue analgesia when the Numeric Rating Scale (NRS) pain score was ≥ 4. Group C (control group) received IV-PCA by morphine 3 mg IV when NRS pain score was ≥ 4 and repeated 1/2 mg if still pain score was recorded ≥ 4 for 15 min. Pain was measured on NRS at 2 , 4 , 8, and 12 h as well as the postoperative heart rate (HR) and mean arterial blood pressure (MAP). Complications were noted, Results: Time to first analgesic request was substantially prolonged in Group ESPB compared to Group C (P < 0.001). Total postoperative consumption of morphine in 1st 48 h and postoperative nausea and vomiting were substantially reduced in Group ESPB compared to Group C (P < 0.05). NRS pain scores, postoperative HR and MAP measurements were substantially reduced at 2, 4, 8, and 12 h in Group ESPB than Group C (P < 0.05). Bradycardia and hypotension varied insignificantly different between both groups. Respiratory depression and urinary retention did not occur in any patient in both groups. Conclusions: Compared with IV-PCA administered morphine, bilateral single-injection ESPB was associated with better hemodynamics and analgesic properties, as observed by lower pain scores, less postoperative opioid consumption, and longer time to first analgesic request with good safety profile after radical cystectomy. Keywords: Ultrasound; Erector Spinae Plane Block; Radical Cystectomy; Patient-Controlled Analgesia Citation: Ahmed AM, Tantawy AM, Mahran E, Abd El Galil TE, Abd El Galil AS. Ultrasound-guided erector spinae plane block in radical cystectomy: a randomized controlled study. Anaesth. pain intensive care 2024;28(5):939−944; DOI: 10.35975/apic.v28i5.2568 Received: July 16, 2024; Reviewed: August 05, 2024; Accepted: August 29, 2024