To assess whether users of pancreatic-specific sulphonylureas are at reduced risk of mortality and cardiovascular mortality compared with users of non-specific sulphonylureas, we conducted a cohort study in the population of Tayside, Scotland. We identified 3331 patients with type 2 diabetes who were newly treated with sulphonylureas between 1994 and 2001 and categorized them into those treated with only pancreatic-specific sulphonylureas and those treated with only non-specific sulphonylureas. The risks of mortality and cardiovascular mortality were compared in a survival analysis. There were 2914 patients treated with pancreatic-specific sulphonylureas only, of which 683 (23.4%) died. Of 186 patients treated with non-specific drugs only, 40 (21.5%) died. After adjusting for confounding factors, the adjusted risk ratios (with 95% CI) for mortality and cardiovascular mortality were 0.84 (0.61 to 1.17) and 0.81 (0.59 to 1.11) among the non-specific users compared with the pancreatic-specific users. This provides no evidence that there are differences between the two sulphonylureas types.