To determine whether the increased prevalence of congestive heart failure in women compared with men undergoing diagnostic cardiac catheterization is the result of a difference in the left ventricular pressure/volume relation, we retrospectively compared the clinical characteristics, left ventricular ejection fraction, and end-diastolic pressure and volume in 586 women and 1081 men undergoing diagnostic coronary angiography and left ventriculography. In comparison with men, women were older (63 vs 60 years; p = 0.0001) and had more hypertension (41% vs 31%; p = 0.0001), diabetes (18% vs 12%; p = 0.003), and symptoms of congestive heart failure (13% vs 10%; p = 0.05). In spite of this, women had a better mean left ventricular ejection fraction (61% vs 56%; p = 0.0001) and less prevalent three-vessel disease (23% vs 34%; p = 0.0001). Left ventricular end-diastolic volume index was smaller in women compared with men (73 vs 79 ml/m2; p = 0.0001) in spite of having similar left ventricular end-diastolic pressure. When patients were stratified according to left ventricular end-diastolic pressure, women had a significantly smaller end-diastolic volume than men did when left ventricular end-diastolic pressure was > or = 18 mm Hg (74 vs 86 ml/m2; p = 0.0001). In a multivariate analysis, female sex remained an independent predictor of congestive heart failure (odds ratio 1.72, 95% confidence interval 1.11 to 2.66, p = 0.02). This study suggests that diastolic dysfunction is one mechanism for the paradox of more frequent heart failure symptoms in spite of better preserved left ventricular systolic function in women. Sex appears to influence the pattern of myocardial dysfunction in patients with known or suspected coronary artery disease, but the basis for this observation remains speculative.