Studies have reported a possible link between cocaine use and risk for cardiovascular events. The aim of this study was to examine the association between self-reported cocaine use and physician-diagnosed myocardial infarction (MI) in the Third National Health and Nutrition Examination Survey (NHANES III), conducted from 1988 to 1994. Odds ratios (ORs) were estimated using logistic regression models adjusted for age and additionally for gender, race, and other MI risk factors, which accounted for the complex sampling design. In the group aged 18 to 59 years, there was no statistically significant association between any exposure to cocaine and MI (age-adjusted OR 1.56, 95% confidence interval [CI] 0.44 to 5.50, p = 0.48; multivariate-adjusted OR 1.06, 95% CI 0.30 to 3.73, p = 0.92). Participants who reported using cocaine >10 times had a nonsignificant higher prevalence of MI (age-adjusted OR 3.13, 95% CI 0.80 to 12.25, p = 0.10; multivariate-adjusted OR 1.84, 95% CI 0.46 to 7.29, p = 0.40). However, participants aged 18 to 45 years who reported >10 occasions of cocaine use had a significantly elevated prevalence of MI in age-adjusted models (OR 4.60, 95% CI 1.12 to 18.88, p = 0.035). The association was attenuated in multivariate-adjusted models (OR 3.84, 95% CI 0.98 to 15.07, p = 0.054). The lifetime prevalence of cocaine use increased from 14% in NHANES III to 19% in NHANES 2005-2006. In conclusion, these data support a substantial association between cocaine use and MI; the temporal trend in cocaine use may increase the occurrence of MI, particularly in younger populations. © 2008 Elsevier Inc. All rights reserved.