Subclinical myocardial and vascular dysfunctions occur in subjects with obesity. We investigated whether these changes were reversible with weight loss due to lifestyle intervention. Quantitative assessment of myocardial and vascular functions was performed at baseline and after a minimum of 8 weeks of a lifestyle intervention program in 106 subjects with significant risk factors but no history of cardiovascular disease and normal ejection fractions. Myocardial function was assessed using strain rate, strain, regional myocardial systolic velocity, and diastolic velocity (e(m)). Myocardial reflectivity was assessed by calibrated integrated backscatter. Vascular function was assessed using brachial arterial reactivity and arterial compliance. Exercise capacity was measured by peak oxygen consumption per unit time (VO(2)). Weight loss (-4.5 +/- 2.0%) was achieved by 48 subjects, and 58 maintained or increased weight (+1 +/- 1.5%, p <0.001). Compared with the stable weight group, the weight loss group showed significant improvement in brachial arterial reactivity (8.6 +/- 4.9% vs 6.7 +/- 4.9%, p <0.05), e(m) (6.4 +/- 1.9 vs 5.5 +/- 1.9 cm/s, p <0.01), and reflectivity (calibrated integrated backscatter, 18.3 +/- 4.9 vs 16.2 +/- 5.2 dB, p <0.01). The magnitude of weight change correlated with changes in e(m) (r = 0.36) and calibrated integrated backscatter (r = 0.33). The change in e(m) correlated with peak VO(2) (r = 0.38, p <0.001) and was an independent predictor for peak VO(2) even after adjustment for age and body mass index in a multivariate model (R(2) = 0.45, p <0.001). Weight loss was not associated with a significant change in systolic parameters (regional myocardial systolic velocity, global strain, and strain rate) or arterial compliance.