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BACKGROUND Celiac plexus neurolysis (CPN) has been used to control pancreatic cancer (PC) pain, up to our knowledge, there is no study compared intraoperative CPN and computed tomography (CT)-guided techniques. OBJECTIVES To compare the effects of intraoperative and CT-guided CPN in unresectable PC on pain intensity and analgesic requirements. METHODS A total of 90 patients were enrolled in this prospective, randomized, open label, controlled, non-inferiority study, 20 patients were excluded or lost to follow up. The patients were randomly allocated to either intraoperative or CT-guided CPN group. A mixture of 20 mL ethanol 90%, 100 mg lignocaine and 5 mg dexamethasone was infused on each side of the aorta in both groups. Visual analogue score (VAS) and oral daily tramadol consumption were recorded at day 7, 14, 30, 60, 120 and 180 days after intervention. Occurrence of any intervention related complications were reported. RESULTS Median VAS was similar in both intraoperative and CT-guided CPN groups from day 7 up to 180 days after intervention. The median daily analgesic consumption of oral tramadol (mg) was comparable in both intraoperative and CT-guided CPN groups after intervention at day 7 (50 versus 50), day14 (50 versus 50), day 30 (50 versus 50), day 60 (50 versus 50), day 120 (100 versus 75) and day 180 (100 versus 100). The incidence of diarrhea, vomiting, hypotension and back pain was similar in both groups. CONCLUSION Intraoperative CPN is non-inferior to CT-guided CPN as both techniques were similarly associated with reduced pain severity and analgesics requirements.