Background: Laparoscopic cholecystectomy (LC) is the standard treatment for gallbladder diseases, traditionally performed under general anesthesia (GA). However, spinal-epidural anesthesia (SEA) has emerged as a potential alternative due to its advantages in postoperative recovery, reduced nausea, and improved pain control. Despite these benefits, the choice between SEA and GA remains debated in clinical practice. Objective: This study aims to compare the perioperative and postoperative outcomes of LC performed under SEA versus GA, focusing on pain management, complications, and recovery parameters. Methods: A prospective randomized controlled trial was conducted at a tertiary care hospital from September 2023. A total of 97 patients were randomly allocated to undergo LC under SEA [n=48]or GA[ n=49]. Inclusion criteria included ASA I-II status, age 18-65 years, and BMI ≤30 kg/m². Perioperative parameters, postoperative pain (Visual Analog Scale), complications, and hospital stay duration were assessed. Statistical significance was determined using appropriate tests, with an interim analysis performed after the first 100 patients. Results: Baseline characteristics were comparable between groups. Median operative time was 45 minutes for SEA and 47 minutes for GA. SEA patients experienced significantly lower postoperative pain scores at all time points (p < .001). The incidence of postoperative nausea and vomiting was slightly higher in the GA group (16.7%) than in the SEA group (14.3%). Urinary retention was observed only in the SEA group (6.1%), while dizziness and sinus tachycardia were exclusive to GA (2.1% each). The median hospital stay was one day for both groups. Conclusion: SEA provides superior postoperative pain control compared to GA while maintaining comparable operative and anesthesia durations. Although SEA was associated with urinary retention, GA had a higher incidence of nausea, dizziness, and tachycardia. These findings support SEA as a viable alternative to GA in LC, particularly for patients prioritizing pain reduction and enhanced recovery.