The renin-angiotensin system may play a pivotal role in reperfusion ventricular arrhythmias (RVA). The purpose of this study was to investigate the association between angiotensin-converting enzyme (ACE) gene polymorphism and RVA in patients with acute myocardial infarction (AMI) in a case-control study. Patients who had undergone successful coronary intervention for AMI were enrolled (n= 127, male/female: 97/30, mean age, 62.6 years). The incidence of RVA was continuously monitored by ECG at a coronary care unit. The severity of ventricular arrhythmias was evaluated in terms of the Lown's grade and patients with a high risk of ventricular arrhythmias that may cause sudden cardiac death (Lown's grade > or =2) within 5 h of coronary intervention were defined as cases (n=59), and otherwise as controls (n=68). A receiver operating characteristic curve was used to determine the discriminatory ability of continuous variables and to produce dummy variables for use in a logistic regression analysis. Cases had a significantly higher body mass index, higher maximal levels of serum creatine kinase, and a shorter time preceding coronary intervention than controls. The severity of coronary atherosclerosis was similar between the 2 groups. The frequency distribution of ACE genotypes in cases differed from that in controls (II/ID/DD: 22.0%/52.6%/25.4% vs 44.1%/41.4%/14.7%, p<0.05, by the Mantel-Haenzel chi-square test). The ACE-D allele had additive and dominant effects with regard to the occurrence of significant ventricular arrhythmias after adjusting for other risk factors. The ACE-D allele may play a pivotal role in sudden cardiac death in patients with AMI.