Angiotensin-converting enzyme (ACE) inhibitors and diuretics have been associated with acute pancreatitis. We quantified the risk of acute pancreatitis associated with the use of antihypertensive medication in the European study on drug-induced acute pancreatitis (EDIP). The EDIP study is a multicenter population-based European case-control investigation of the association between drug use and acute pancreatitis. Patients between 40 and 85 years of age hospitalized for acute pancreatitis were included in the study between 1 October 1994 and 31 December 1998. For each case, age- and gender-matched community controls were recruited. Detailed information on drug use and potential confounders (e.g. comorbidity, alcohol use) was obtained through a structured interview. In all, 724 patients with acute pancreatitis and 1791 community controls were identified and interviewed. Use of ACE inhibitors in the week prior to the index date was associated with an increased risk of acute pancreatitis (adjusted odds ratio 1.5; 95% CI: 1.1-2.2). The risk of acute pancreatitis associated with ACE inhibitors increased with higher daily doses and was highest in the first 6 months of therapy. Calcium channel blockers increased the risk of acute pancreatitis (adjusted odds ratio 1.5; 95% CI: 1.1-2.1) without an apparent dose- or response relationship. Loop and thiazide diuretic use was not associated with an increased risk of acute pancreatitis. Potassium-sparing diuretics elevated the risk of acute pancreatitis, albeit non-significantly. Use of ACE inhibitors is associated with a modest increase in the risk of acute pancreatitis during the first months of treatment.