We analysed common variants of eight genes implicated previously as risk factors for coronary heart disease or myocardial infarction (MI) in a cross-sectional study on patients with a history of MI and in carefully matched controls from the Finnish population. The most common low density lipoprotein receptor mutations in Finland were also included in our analysis. Multiplex genotyping of the target genes was performed using a specific and efficient array-based minisequencing system. The 4G allele of the plasminogen activator inhibitor gene (P < 0.05) and the PlA2 allele of the glycoprotein IIIa gene (P < 0.01) were associated with an increased risk of MI in our study population. We analysed the combined effect of these risk alleles and found that the concurrent carrier status of the two genetic variants conferred a high risk for the development of MI in our sample (OR = 4.5, P = 0.001), which was particularly prominent in male subjects (OR = 6.4, P = 0.0005). This study demonstrates the application of a new powerful tool for genome analysis to yield information on the inherited determinants of susceptibility to MI. The observation of two separate genes contributing an additive risk of developing MI exemplifies the advantages of multiplex analysis of genetic variation.