This study examined whether the combination of alternate day fasting (ADF) plus exercise produces superior changes in body composition and plasma lipid levels when compared to each intervention alone. Obese subjects (n = 64) were randomized to 1 of 4 groups for 12 weeks: 1) combination (ADF plus endurance exercise), 2) ADF, 3) exercise, or 4) control. Body weight was reduced (P < 0.05) by 6 ± 4 kg, 3 ± 1 kg, and 1 ± 0 kg in the combination, ADF, and exercise groups, respectively. Fat mass and waist circumference decreased (P < 0.001), while lean mass was retained in the combination group. Low-density lipoprotein (LDL) cholesterol decreased (12 ± 5%, P < 0.05) and high-density lipoprotein (HDL) cholesterol increased (18 ± 9%, P < 0.05) in the combination group only. LDL particle size increased (P < 0.001) by 4 ± 1 Å and 5 ± 1 Å in the combination and ADF groups, respectively. The proportion of small HDL particles decreased (P < 0.01) in the combination group only. These findings suggest that the combination produces superior changes in body weight, body composition, and lipid indicators of heart disease risk, when compared to individual treatments.