Background: Extensive surgical dissection, hemodynamic alterations associated with cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) make pain management challenging. We hypothesized that infusions of intravenous lignocaine and fentanyl provide comparable analgesia to epidural ropivacaine and fentanyl in these patients. Methods: Fifty patients scheduled to undergo CRS and HIPEC were enrolled in the study. The patients in group IV (Intravenous) received a bolus dose of 1.5 mg/kg lignocaine over 15 min, starting approximately 15 min before the surgical incision and fentanyl 0.5 mcg/kg, about 2 min before the surgical incision, following which patient received lignocaine infusion at 1 mg/kg/hr and fentanyl infusion at 0.5 mcg/kg/hr intraoperatively. Patients in group EPI (Epidural) received 6 mL of Ropivacaine 0.2% and fentanyl (2mcg/mL) approximately 15 min before surgical incision, followed by continuous infusion at the rate of 5 mL/hr. The procedure for induction and maintenance of anesthesia was standardized for both groups. In the postoperative period, the infusion of analgesics was reduced to half the intraoperative rates and continued for 24 h. Results: Demographic profile and clinical parameters were comparable between both groups (p > 0.05). There was no difference between the number of fentanyl doses given in the IV group [Langenbecks Arch Chir 373(3):189–196, 4, IQR (2–11)] and the EPI group [Reg Anesth Pain Med 35(4):370–376, 12, IQR (5–21)] in the postoperative period (p = 0.229). The need for intraoperative rescue analgesia was comparable among the groups (p = 0.882). Conclusion: The two techniques, epidural (ropivacaine and fentanyl) and IV (lignocaine and fentanyl) infusions, provide comparable analgesia in patients undergoing CRS and HIPEC. Trial registration number: CTRI/2020/08/027052 dated 09/08/2020. [ABSTRACT FROM AUTHOR]