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Current data regarding an association between cholelithiasis, cholecystectomy, or gastrectomy and pancreatic cancer are conflicting. We evaluated the frequency with which these factors were present in 720 patients with newly diagnosed pancreatic cancer and in 720 matched controls. All subjects were interviewed personally and in detail about their clinical history. Cholelithiasis was present in 126 patients with pancreatic cancer (17.5%) and in 95 controls (13.2%), constituting a statistically significant association (odds ratio, 1.39; 95% confidence interval, 1.04–1.86); however, considering only the patients and controls in whom the diagnosis of cholelithiasis was made more than one year before cancer diagnosis or interview, the association was no longer significant (odds ratio, 1.04; 95% confidence interval, 0.75–1.44). Cholecystectomy had been performed in 93 patients with pancreatic cancer (12.9%) and in 71 controls (9.9%). When all subjects were considered, the odds ratio was mildly, although not significantly, increased (odds ratio, 1.35; 95% confidence interval, 0.97–1.87); when only subjects who underwent cholecystectomy one year or more before the cancer diagnosis or interview were considered, the odds ratio fell to unity. Gastrectomy had been performed in 28 patients with pancreatic cancer (3.9%) and in 25 controls (3.5%); analysis revealed no significant association between these two factors (odds ratio, 1.14; 95% confidence interval, 0.64–2.05). In conclusion, our study, one of the largest on this topic, has found no evidence for an association between cholelithiasis, cholecystectomy, or gastrectomy and pancreatic cancer.