Pancreatic pseudocyst (PP) is the commonest cystic lesion of the pancreas. Internal drainage of PPs can be accomplished by traditional open or recently by minimally invasive laparoscopic or endoscopic approaches. We aimed to evaluate and compare the clinical outcomes after endoscopic, laparoscopic, and open drainage. Seventy-one patients with PP underwent endoscopic (n = 35), laparoscopic (n = 4), and open surgical drainage (n = 32). The primary outcome was the success rate. The secondary outcomes were the estimated blood loss, operative time, opioid requirement, morbidity and mortality, length of hospital stay, and recurrence rate. The primary success rate was significantly higher for laparoscopic and open groups than for the endoscopic group, but the overall success rate was equivalent across the groups. There were no significant differences in the morbidity, mortality, requirement of blood transfusion, reinterventions, and recurrence rate between the groups. Endoscopic drainage revealed significantly lower blood loss, operative time, opioid requirement, and hospital stay in comparison to open and laparoscopic drainage. Minimally invasive therapeutic techniques, whether endoscopic or laparoscopic for treatment of PP could be considered valuable, competitive, and promising alternatives for open surgery. Moreover, it is less invasive with less hospitalization and rapid return to work.