Complex pyogenic liver abscess (CPLA) is a rare fatal disease if untreated. Complex pyogenic liver abscess is a multilocular abscess more than 5 cm in diameter. Pyogenic liver abscess (PLA) is mainly treated by percutaneous aspiration or drainage under antibiotic cover. Surgical drainage is indicated if interventional radiology fails, if ruptured, or if associated with biliary or intra-abdominal pathology. Laparoscopic drainage is a promising management option. Aim: To evaluate the safety and efficacy of laparoscopic drainage as a management of complex pyogenic liver abscesses in comparison to open surgical drainage. Materials and methods: Combined retrospective and prospective comparative study of 48 patients having complex PLA who were admitted to NHTMRI and managed by either laparoscopic drainage or open surgical drainage from January 2012 to January 2020 as regards results, complications, perioperative morbidity, mortality, and possible recurrence. Twenty-six patients were managed by open drainage, and 22 patients by laparoscopic drainage. Culture sensitivity of pus was done for all patients. Patients having small, solitary, and unilocular PLA that responded to antibiotic treatment or/and percutaneous drainage were excluded. All patients were subjected to full clinical assessment, laboratory investigations, ultrasonography, computed tomography, or magnetic resonance images for the abdomen and pelvis. Results: Forty-eight patients having complex PLA with a median age of 54.5 years were managed by either laparoscopic drainage (22 patients) or open surgical drainage (26 patients). The operation time and hospital stay were less, and oral feeding was started earlier in laparoscopic group. Wound infection was higher in open drainage group. Abscess recurrence occurred once in laparoscopic group and once in open surgery group, and both were successfully treated with percutaneous drainage. One laparoscopic operation was converted to open. Conclusion: Both laparoscopic and open surgical drainage of PLA are safe and effective. Laparoscopic drainage has less operative time, morbidity, and hospital stay; however, open drainage is considered the management of choice for patients with severe sepsis or failed percutaneous drainage.