A C1019T polymorphism in the human connexin37 (hCx37) gene has been associated with cardiovascular risk, but it remains debatable whether the 1019C or the 1019T allele carries this risk. Here, we investigated whether these allelic variants are differentially predictive of increased risk for coronary artery disease (CAD) and myocardial infarction (MI). A total of 781 Swiss participants, including 597 patients diagnosed with CAD, 50% who reported previous MI, and 184 control subjects were genotyped. Patients in the +CAD group had a higher frequency of the Cx37-1019C allele (70.3% versus 65.0%, p=0.004). Multivariate analysis showed that the hCx37-C1019T polymorphism is an independent predictor of CAD (odds ratio=2.13, confidence interval=1.31-3.46 and p<0.01). Moreover, this polymorphism is not associated with any of the other characteristics examined, including gender, age, body-mass-index, diabetes, total/HDL/LDL-cholesterol, triglycerides, apoA-I, apoB, hypertension and cigarette smoking. In comparison with the -CAD group, we observed an increase of the Cx37-1019C allele in the +MI +CAD subgroup (71.2% versus 65.0%, p=0.002) but not in the -MI +CAD subgroup. Allelic frequency comparisons of these three subgroups predicted that this polymorphism is also an independent risk factor for MI. In conclusion, our results reveal the importance of screening the Cx37-1019C allele for both CAD and MI risk assessments.