This study evaluates the association between the presence of diagonal earlobe creases (ELC) and coronary artery disease (CAD). One thousand four hundred twenty-four patients (760 men and 664 women, aged 30 to 80 years) were examined for the presence of ELC and classified into 2 groups: group I control--1,086 consecutive patients who denied symptoms of myocardial ischemia and were admitted to a general hospital for other reasons; group II CAD--338 patients with documented CAD (presence of > or = 70% coronary diameter stenosis at angiography). ELC was present in 304 patients (28%) in group I and 220 (65%) in group II (p < 0.0001). The patients were stratified in age groups to isolate the influence of age because the prevalence of ELC and CAD increased with advancing age (p < 0.0001 for both). This association remained statistically significant in all decades, except for patients aged > 70 years. To further remove the confounding effect of different age and sex distributions between the groups, a direct adjustment of the ELC prevalence was performed. When adjusted for age and sex, the prevalence of creases was still 58% higher in patients with CAD than in control subjects (p < 0.001). The presence of ELC was also related to the extent of CAD as measured by the number of major arteries narrowed (p = 0.015). The observed sensitivity of the sign for the diagnosis of CAD was 65%, the specificity 72%, the positive predictive value 42% and the negative predictive value 87%.