A common 825C>T polymorphism in exon 10 of the gene for the beta-3 subunit of heterotrimeric G-proteins, GNB3, has been associated in some studies with traits of the metabolic syndrome as well as coronary artery disease (CAD), but these associations were refuted by other studies. To investigate the role of GNB3 gene variations in CAD and myocardial infarction (MI), we determined five GNB3 polymorphisms (-1429G>A, IVS5 +41G>A, 657T>A, 814G>A and 825C>T) in the Ludwigshafen Risk and Cardiovascular Health (LURIC) cohort, including 2575 patients with angiographically documented CAD and 731 individuals in whom CAD had been ruled out by angiography. None of the GNB3 polymorphisms was associated with CAD, MI, diabetes, hypertension, blood pressure, body weight or body mass index. We conclude that a major contribution of GNB3 gene variants to CAD or MI risk is unlikely.