Extreme obesity is known to be associated with left ventricular (LV) systolic dysfunction. The relation of lesser degrees of obesity and LV systolic function is controversial. This study assessed the relation between body mass index (BMI; weight in kilograms divided by height in meters squared) and the LV ejection fraction (EF) and volumes in 1,806 subjects with normal technetium-99m sestamibi myocardial perfusion imaging results. BMI was evaluated as a continuous and a categorical variable (normal >18.5 and <25, overweight > or =25 and <30, obese > or =30 and <35, and severely obese > or =35 kg/m(2)). The prevalence of an EF < or =50% was similar in normal, overweight, obese, and severely obese subjects. On univariate analysis, only severely obese women had mildly reduced LVEFs. LV end-diastolic and end-systolic volumes increased linearly from normal to obese men and women, respectively (each p <0.01). On multiple linear regression analysis (R = 0.5, p <0.001), BMI (p = 0.03) and diabetes (p <0.001) influenced the EF adversely, whereas age and female gender were protective (p <0.001). However, on gender-stratified analysis, diabetes, not BMI, independently predicted the EF in men and women. BMI remained an independent predictor of greater end-diastolic volumes in men and women (p <0.01) even after accounting for co-morbidities. In conclusion, mild obesity was associated with LV dilatation, but the LVEF was preserved even with severe obesity. Weight control may be recommended to reduce the incidence of obesity-related co-morbidities and their impact on adverse LV remodeling.