Background: Basic and clinical studies suggest that statins may prevent and even ameliorate acute pan- creatitis. The present study was to evaluate whether statin decreases the risk of acute pancreatitis in patients undergoing endoscopic ultrasound-guided fine-needle aspiration of pancreatic cysts.Methods: Out of 456 patients with pancreatic cysts referred to our center between 2006 and 2018, 365 were finally included in analyses: 86 were treated with statins and 279 were not at the time of endo- scopic ultrasound fine-needle aspiration. We compared the acute pancreatitis incidence between the two groups, and we also compared other complications such as bleeding and infections. Results: Median age was 64 years [interquartile range (IQR) 62-69] and median cyst size was 24 mm (IQR, 21-29). The most frequent histology was intraductal papillary mucinous neoplasm (45.3％ and 42.3％ in the two groups, respectively; P = 0.98). All 13 patients experiencing post-endoscopic ultrasound acute pancreatitis were from the control group (4.7％), of which 3 were classified as severe pancreatitis. None of statin users developed post-procedural acute pancreatitis (odds ratio: 0.15; 95％ confidence interval: 0.03-0.98; P = 0.03). No difference was registered with regard to severe pancreatitis and other complications. Conclusions: Statins exert a beneficial role in preventing acute pancreatitis in patients with pancreatic cysts undergoing endoscopic ultrasound-guided fine-needle aspiration. If confirmed in prospective trials, our findings may pave the way to an extensive use of statins as prophylactic agents in pancreatic inter- ventional endoscopy.