Numerous studies suggest that the prevalence of depression is greater among cardiac patients than in the general population. However, little attention has been paid to the possibility of genetic contributions to depressive symptoms in cardiac patients. We conducted a candidate gene study focusing on genes related to inflammation, platelet aggregation, endothelial function and omega-3 fatty acid metabolism as predictors of depressive symptoms among 977 participants with established cardiovascular disease. Results suggested that genetic variation related to endothelial dysfunction is predictive of depressive symptoms and that endothelial dysfunction may be a novel mechanism contributing to depressive symptoms among cardiac patients. © 2008 Wiley-Liss, Inc.