There are few data about the incidence, determinants, and clinical course of in-hospital repeat acute myocardial infarction (RE-AMI) after an index AMI. From June 1994 to June 1998, 22,613 patients with AMI as an index event were registered by the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) and Myocardial Infarction Registries (MIR). Of these, 1,071 (4.7%) had a RE-AMI. For the index event, 9,143 patients (40.5%) were treated with thrombolysis, 1,707 (7.5%) with primary angioplasty, and 443 (2.0%) with a combination of both. Multivariate analysis showed that previous AMI (odds ratio [OR] 1.59; 95% confidence intervals [CI] 1.35 to 1.86), age >70 years (OR 1.57; 95% CI 1.36 to 1.81), diagnostic first electrocardiogram (OR 1.37; 95% CI 1.19 to 1.59), and female gender (OR 1.14; 95% CI 1.05 to 1.32) were independently associated with a higher incidence of RE-AMI. The incidence of RE-AMI was higher when patients received thrombolysis (OR 1.36; 95% CI 1.15 to 1.61), and it was lower when they underwent primary angioplasty (OR 0.74; 95% CI 0.53 to 1.03) or received beta blockers (OR 0.84; 95% CI 0.72 to 0.97). Patients with RE-AMI had higher hospital mortality compared with those without RE-AMI (OR 4.35; 95% CI 3.83 to 4.95). Multivariate logistic regression analysis showed an independent association of RE-AMI with in-hospital death (OR 6.60; 95% CI 5.61 to 7.70), repeat revascularization (OR 2.91; 95% CI 2.42 to 3.50), low workload capacity on the bicycle ergometry test (OR 2.17; 95% CI 1.71 to 2.76), and ejection fraction <40% (OR 1.72; 95% CI 1.38 to 2.14) at discharge. Thus, RE-AMI occurs in 4.7% of patients after an AMI. Previous AMI, age >70 years, diagnostic first electrocardiogram, and female gender are independent determinants for RE-AMI. Thrombolysis is associated with a higher and beta blockers with a lower incidence of RE-AMI. Once a RE-AMI occurs, it is a strong predictor of in-hospital mortality and morbidity.