BACKGROUND: Internal drainage of pancreatic pseudocysts can be accomplished by traditional open or minimally invasive laparoscopic or endoscopic approaches. This study aimed to evaluate the primary and overall success rates and clinical outcomes after laparoscopic, endoscopic, and open pancreatic cystgastrostomy for pancreatic pseudocysts. METHODS: Records of 83 patients undergoing laparoscopic (n = 16), endoscopic (n = 45), and open (n = 22) pancreatic cystgastrostomy were analyzed on an intention-to-treat basis. RESULTS: There were no significant differences (p < 0.05) in the mean patient age (years), gender, body mass index (BMI) (kg/m(2)), etiology of pancreatitis (% gallstone), or size (cm) of pancreatic pseudocyst between the groups. Grade 2 or greater complications occurred within 30 days of the primary procedure for 31.5% of the laparoscopic patients, 15.6% of the endoscopic patients, and 22.7% of the open patients (nonsignificant differences). The follow-up evaluation for 75 patients (90.4%) was performed at a mean interval of 9.5 months (range, 1-40 months). The primary compared with the overall success rate, defined as cyst resolution, was 51.1% vs. 84.6% for the endoscopic group, 87.5% vs. 93.8% for the laparoscopic group, and 81.2% vs. 90.9% for the open group. The primary success rate was significantly higher (p < 0.01) for laparoscopic and open groups than for the endoscopic group, but the overall success rate was equivalent across the groups (nonsignificant differences). Primary endoscopic failures were salvaged by open pancreatic cystgastrostomy (n = 13), percutaneous drainage (n = 3), and repeat endoscopic drainage (n = 6). CONCLUSIONS: Laparoscopic and open pancreatic cystgastrostomy both have a higher primary success rate than endoscopic internal drainage, although repeat endoscopic cystgastrostomy provides overall success for selected patients.