Abstract Background Poorly controlled acute pain after abdominal surgery is associated with a variety of unwanted postoperative consequences, including patient suffering, distress, respiratory complications, delirium, myocardial ischemia, prolonged hospital stay and an increased likelihood of chronic pain. Aim of the Work The aim of this study is to assess the postoperative analgesic efficacy of quadratus lamborum plain block compared to intraperitoneal and periportal infiltration with bupivacaine after laparoscopic cholecystectomy regarding the pain relief, effect on hemodynamics, requirement of first supplemental doses of analgesia and total number of doses received. Patients and Methods The study was conducted on 70 randomly chosen patients aged 20 to 60 years, American Society of Anesthesiologists (ASA) class I or II scheduled for elective laparoscopic cholecystectomy in Ain Shams University Hospitals after approval of the medical ethical committee. They were allocated in two groups of 35 patients each: QL block Group, intraperitoneal and periportal infiltration Group: Results Patients receiving QL block had significantly lower pain scores at rest for 6 hrs and decrease total need of analgesic in first 24 h post operative compared with patients who received Intraperitoneal and port sites infiltration. Conclusion Quadratus Lumborum block was effective in reducing postoperative pain scores for 6 hours and lower total 24 hrs postoperative opioid and analgesic consumption after laparoscopic cholecystectomy under general anesthesia, compared to intraperitoneal and port sites infiltration. This technique can be a promising mode of postoperative analgesia where epidural catheter insertion is contraindicated.