Objective To investigate the safety and efficacy on early treatment of large pancreatic pseudocyst by endoscopic ultrasound (EUS)-guided transgastric drainage. Methods The clinical data of 23 cases of large pancreatic pseudocyst treated with EUS-guided transgastric drainage from 2003 to 2008 was retrospectively analyzed. Results All were of single pseudocyst. Pseudocyst was present in the head of the pancreas in 3 cases, in the body of the pancreas in 11 cases, in the tail of the pancreas in 9 cases. Mean diameter of pancreatic pseudocysts was 11 cm( range 8 - 18 cm ). The interval between the finding of pseudocysts and EUS-guided transgastric drainage ranged 17 -65 d, averaging 31 d. Two had postoperative infection of the pseudocyst, one received percutaneons external drainage and the other one received surgical internal drainage. Three had postoperative gastrointestinal bleeding and were treated with antacid and hemostatic drugs. Patients were examined by CT two to three months later. Pancreatic pseudocysts disappeared completely in 6 cases and significantly shrank in the rest. The clinical symptoms of all patients,such as abdominal pain, abdominal bloating were significantly relieved. All patients were followed-up for 1 year, there was no pseudocyst recurrence, ulcer,bleeding or infection. Conclusions Early treatment of large pancreatic pseudocyst by EUS-guided transgastric drainage is safe and effective.