BACKGROUND Hyperinsulinemia has been associated with obesity, hypertension, diabetes, and coronary artery disease. However, it is not clear whether hyperinsulinemia by itself is a risk factor for coronary artery disease in the absence of obesity, diabetes, and hypertension. Therefore, we conducted a study to evaluate the role of hyperinsulinemia in coronary artery disease in the absence of diabetes, hypertension, and obesity. METHODS AND RESULTS A total of 80 cases and 50 controls were studied. Only non-diabetic, normotensive, nonobese men (body-mass index < or = 25) were included. The presence of valvular heart disease or an acute coronary event in the past 6 weeks were exclusion criteria. Serum insulin levels were measured in fasting samples by ELISA assay. The mean fasting insulin was 17.0+/-16.5 microIU/ml and 13.3+/-12.9 microIU/ml in the control and study groups, respectively (reference range 1.5-15.6 microIU/ml). There was no significant association between coronary artery disease and the surrogate markers of insulin resistance, namely, fasting insulin (p value 0.367) and homeostasis model assessment of insulin resistance (p value 0.589). CONCLUSIONS A high-normal fasting insulin level was present in non-diabetic, nonhypertensive, and nonobese men in the Indian population. We suggest that insulin resistance may not per se be an independent risk factor for coronary artery disease. It may be an innocent bystander in coronary artery disease in an obese, hypertensive, and diabetic population. However, due to our small sample size, further studies are required in this direction.