OBJECTIVE Endoscopic drainage of a single pseudocyst is a well-known treatment modality. Its role in the management of multiple pseudocysts is not well established. We evaluated the role of endoscopic transpapillary nasopancreatic drain (NPD) placement in the management of multiple and large pseudocysts. METHODS Over 3 yr (2001-2004), endoscopic transpapillary NPD placement was attempted in 11 patients (age range 12-50 yr, 10 men) with symptomatic communicating multiple pseudocysts of pancreas (three in two and two in nine cases). A 5Fr/7Fr NPD was placed across the most distal duct disruption or into one of the pseudocysts. RESULTS Eight patients had an underlying chronic pancreatitis and three patients had pseudocysts as sequelae of acute pancreatitis. The size of pseudocysts ranged from 2 to 14 cm (mean 7.5 cm). Eight patients (72.7%) had at least one pseudocyst more than 6 cm in size. Nine patients had a partial disruption and two patients had complete disruption of the pancreatic duct. The NPD was successfully placed in 10 of 11 (90.9%) patients. Postprocedure acute febrile illness in one patient was the only complication noted, which responded to intravenous antibiotics. All pseudocysts resolved in 4-8 wk in 7 of 7 patients with successful bridging of the most distal ductal disruption. There was no recurrence of the pseudocysts in a mean follow-up of 19.4 months. Two patients, in whom there was a complete disruption and the NPD could not bridge the disruption, required surgery for the nonresolution of pseudocysts. In one patient with partial ductal disruption that could not be bridged, there was complete resolution of one pseudocyst and a decrease in the size of the other pseudocyst from 12 to 4 cm. The NPD was replaced by a stent and both the pseudocysts resolved in 20 wk. CONCLUSIONS Endoscopic transpapillary NPD placement is a safe and effective modality for the treatment of multiple and large pseudocysts, especially when there is partial ductal disruption, and the disruption can be bridged.