We studied 5 functional hemostatic polymorphisms in 281 patients with premature myocardial infarction and in 530 control subjects. The role of these polymorphisms when analyzed independently is small, if any. However, the simultaneous combination of factor XIII and prothrombin polymorphisms exacerbated the risk. (OR=12.12; p=0.028). Moreover, combinations of factor V Leiden with prothrombin, and factor XII with prothrombin polymorphisms were only identified in patients. Our results support the relevance of gene-gene interactions in myocardial infarction.