Objective To investigate the value of endoscopic ultrasonography (EUS) and abdominal CT (CT) in diagnosis of periampullary lesions and to make comparison between the two procedures. Methods The patients suspected of surrounding lesions of ampullary from 2009 to 2013 in our hospital were included in this study. All the patients received both EUS and abdominal CT. The accuracy rate of these two examination methods was compared. Results 151 patients were confirmed as surrounding lesions of ampullary, including choledocholithiasis, ampullary tumors, ampullary inflammation, tumors of the pancreatic head and pancreatic cysts. The accuracy rate of these diseases was 83.6%, 90.6%, 6.5%, 100.0%, and 100.0%for EUS;while was 52.2%, 56.3%, 43.5%, 91.3%, and 100.0%for abdominal CT. The tatal accuracy rate for diagnosing periampullary lesions by EUS was significantly higher than that by abdominal CT (84.1% vs. 59.6%). Conclusions Endoscopic ultrasonography has higher value in diagnosis of periampullary lesions, and its accurate rate was higher than that of abdominal CT.