The association of epilepsy with risk of acute myocardial infarction (AMI) remains uncertain, and its association with myocardial infarction prognosis has not been evaluated. In this study, we performed a population-based case-control study that included 1799 cases with first AMI and 2339 controls, frequency matched by age, sex and hospital catchment area. A history of epilepsy was identified using the Swedish hospital discharge registry. Information on lifestyle and biomarkers was determined from questionnaires and standardized clinic examinations. The cohort of cases was followed for 8 years to evaluate the relationship between epilepsy and post AMI prognosis. A diagnosis of epilepsy was associated with higher risk of incident AMI, with an odds ratio (OR) of 4.92 [95% confidence interval (CI) 2.34-10.31] after adjustment for age, gender, hospital catchment area, and education. There was a graded positive relation between number of hospitalizations for epilepsy and risk of AMI. Adjustment for smoking and levels of tissue plasminogen activator (tPA)/plasminogen activator inhibitor 1 (PAI-1) complex, von Willebrand factor and homocysteine weakened, and adjustment for high-density lipoprotein (HDL) and fibrinogen strengthened, the relationship between epilepsy and AMI. The OR for epilepsy was 4.83 (95% CI 1.62-14.43) when age, gender, hospital catchment area, education and established, clinically relevant AMI risk factors, i.e. diabetes mellitus, smoking, hypertension, physical activity, obesity, high-density lipoprotein, total cholesterol and alcohol consumption were simultaneously controlled for. Epilepsy was also associated with AMI prognosis. Multivariable adjusted hazard ratios for total and cardiac mortality and for a combined outcome of cardiac death and non-fatal reinfarction, heart failure and stroke during follow up, were 1.95 (0.70-5.43), 3.49 (1.05-11.65) and 2.39 (1.16-4.90), respectively. We conclude that epilepsy might be a risk and an adverse prognostic factor for AMI. Smoking and increase in the level of homocysteine, tPA/PAI-1 complex and von Willebrand factor are candidate mechanisms linking epilepsy to increased AMI risk. Physicians should be aware of the potential cardiovascular implications of epilepsy.