The adipose tissue-derived hormone leptin is among the physiologic processes involved in cardiovascular regulation. The aim of the present study was to elucidate if serum leptin may predict cardiovascular risk, particularly myocardial infarction (MI), in hypertensive men and women. In a prospective study cohort of hypertensive men and women, serum leptin was compared in 171 patients with MI and in 342 matched controls. The mean serum concentration of leptin was 25.1 +/- 20.0 ng/ml in the MI patients and 20.0 +/- 16.6 ng/ml in the controls (p = 0.007). The association between serum leptin and MI was independent of traditional risk factors. Leptin concentrations were higher in women than in men. In women, serum leptin was the most important predictor of MI. The present study indicates that serum leptin is associated with MI in a hypertensive population. Leptin concentrations may be of practical importance when estimating the risk of MI, especially in women, where leptin was found to be the most important predictor for MI.