Background: Post-operative pain management is critical in laparoscopic cholecystectomy to enhance patient recovery and satisfaction. This study compares the efficacy of ultrasound-guided bilateral subcostal transversus abdominis plane (TAP) block and port site infiltration with bupivacaine for post-operative analgesia. Methods: In this prospective, randomized, comparative study, 60(30/30) patients undergoing elective laparoscopic cholecystectomy were randomly assigned to one of two groups: Group A received an ultrasound-guided bilateral subcostal TAP block with 0.25% bupivacaine (20 ml on each side), while Group B received port site infiltration with 0.25% bupivacaine (5 ml per port). The primary outcome was the duration of post-operative analgesia, assessed by the time to first rescue analgesic request. Secondary outcomes included total analgesic consumption in the first 24 hours post-operatively, pain intensity measured by the Visual Analog Scale (VAS) at 1, 4, 8, 12, and 24 hours, and any complications related to the procedures. Results: The TAP block group (Group A) demonstrated a significantly longer duration of analgesia compared to the port site infiltration group (Group B) (p < 0.05). Group A also exhibited lower total analgesic consumption and lower VAS scores at all time points. No significant complications were observed in either group. Conclusion: Ultrasound-guided bilateral subcostal TAP block with bupivacaine provides superior post-operative analgesia compared to port site infiltration in patients undergoing laparoscopic cholecystectomy, with a longer duration of pain relief and reduced analgesic requirements. This technique should be considered a viable option for enhancing post-operative recovery in these patients.