To address the key question of whether using available "cardiogenomic profiles" leads to improved health outcomes (e. g., reduction in rates of myocardial infarction and stroke) and whether these profiles help in making medical or personal decisions. Methods: A targeted evidence-based review based on published Evaluation of Genomic Applications in Practice and Prevention methodologies. Results: No study addressed the overarching question directly. Evidence for the analytic validity of genomic profiles was inadequate for most genes (scale: convincing, adequate, and inadequate), but based on gray data, the analytic sensitivity and specificity might be adequate. For the 29 candidate genes (58 separate associations reviewed), the credibility of evidence for clinical validity was weak (34 associations) to moderate (23 associations), based on limited evidence, potential biases, and/or variability between included studies. The association of 9p21 variants with heart disease had strong credibility with odds ratios of 0.80 (95% confidence interval: 0.77-0.82) and 1.25 (95% confidence interval: 1.21-1.30), respectively, for individuals with no, or two, at-risk alleles versus those with one at-risk allele. Using a multiplicative model, we combined information from 24 markers predicting heart disease and from 13 markers for stroke. The areas under the curves (64.7% and 55.2%, respectively), and overall screening performance (detection rates of 24% and 14% at a 10% false-positive rate, respectively) do not warrant use as stand-alone tests. Conclusion: Even if genomic markers were independent of traditional risk factors, reports indicate that cardiovascular disease risk reclassification would be small. Improvement in health could occur with earlier initiation or higher adherence to medical or behavioral interventions, but no prospective studies documented such improvements (clinical utility). Genet Med 2010:12(12):772-784.