The relative benefits of weight loss (WL) versus aerobic exercise training (AEX) on cardiac risk factors in obese individuals remain controversial. In this study, we examined the effects of the sequential interventions of 9 months of AEX followed by weight loss with continued AEX (AEX + WL) on cardiac risk factors in 21 obese (body fat, 29.5% +/- 0.8%, mean +/- SEM) middle-aged and older men. AEX increased the maximal aerobic capacity ([VO2max] in liters per minute) of these men by 14% (P < .001), with no significant change in weight. AEX did not improve blood pressure (BP) or oral glucose tolerance, and had no significant effect on lipid concentrations. During the AEX + WL intervention, the 21 men lost 8.1 +/- 0.6 kg. Despite continued training, there was no further increase in VO2max during this intervention. Compared with AEX, AEX + WL decreased glucose and insulin responses during the oral glucose tolerance test (OGTT) by 8% (P < .05) and 30% (P < .01), respectively. AEX + WL reduced plasma triglyceride (TG) by 17% (P < .05) and low-density lipoprotein cholesterol (LDL-C) by 8% (P < .01) and increased high-density lipoprotein cholesterol (HDL-C) by 11% (3.7 mg/dL, P < .01). The sequential interventions resulted in a 20% decrease in the LDL-C/HDL-C ratio. The results demonstrate that AEX + WL had a more substantial impact than AEX alone on glucose tolerance and lipoprotein concentrations. Physicians should encourage obese patients to become physically active and lose weight to improve their cardiac risk factor profile.