We compared the heart weights and the incidence of atherosclerotic lesions in trauma fatalities testing positive for cocaine with the hearts of cocaine negative trauma fatalities, with the hearts of decedents dying from cocaine overdose, and with historic controls derived from the literature. There were 116 trauma victims, 83 men and 33 women, aged 20–50 years, and 26 men with cause of death listed as cocaine toxicity. The 32 cocaine (+) male trauma fatalities had a mean age 34 ± 10 years and a mean heart weight of 375 ± 82 grams. The 51 cocaine free males had a mean age 31 ± 9 years, and mean heart weight 337 ± 54 grams (P = .01). Heart weights in the cocaine using group were also significantly greater than historical controls from World War I, Korea, and Vietnam. The incidence of atherosclerotic changes was similar in both groups, but cocaine (+) men had more frequent coronary artery lesions involving multiple vessels (P = .01). Comparisons between 16 cocaine (+) females and 17 cocaine (−) female controls disclosed no significant differences in heart weight or the frequency of atherosclerotic lesions. The 26 men dying of cocaine overdose also had larger hearts than the controls (379 ± 64 g, P = .004), and more severe CAD (30% had involvement of 2 or more vessels, P = .02). The degree of myocardial hypertrophy documented in this study was highly significant, but because the increase is modest (around 10%), it is likely to go unrecognized at autopsy. Cardiac enlargement and coronary artery disease in cocaine users may be much more prevalent than has previously been appreciated, and may be responsible for some unexplained cases of sudden death in cocaine users.