An increased risk of pancreatic cancer following cholecystectomy has been reported in some studies but not in others. In order to settle this question, a population-based cohort consisting of 62,615 patients who had undergone cholecystectomy was followed up for the occurrence of pancreatic and periampullar cancer up to 23 years. After excluding the first year after operation, there were 261 pancreatic cancers vs 216.8 expected [standardized incidence ratio (SIR) = 1.20; 95% confidence interval (CI) = 1.06-1.37]; and 11 periampullar cancers vs 7.2 expected (SIR = 1.52; 95% CI = 0.76-2.72). The increased risk of pancreatic cancer was most prominent up to four years after operation, but was also significantly increased 15 years or more after operation (SIR = 1.35; 95% CI = 1.00-1.78). We conclude that there is a modest excess risk of pancreatic and periampullar cancer following cholecystectomy, most prominent up to four years after operation, but that also exists 15 years or more after operation.