Obesity and depression frequently co-occur, and each increases risk for cardiovascular disease (CVD). This study tested whether a combined treatment, targeting obesity and depression simultaneously, would yield greater improvements in weight, mood, and CVD risk factors than treatments that targeted each disease individually.Seventy-six participants with obesity and major depression were randomly assigned to (1) behavioral weight control (BWC), (2) cognitive behavioral therapy for depression (CBT-D), or (3) BWC combined with CBT-D. Participants were provided 18 group treatment sessions over 20 weeks. Mood, weight, and CVD risk were assessed at baseline and weeks 8 and 20, with a follow-up visit at week 46.At week 20, participants in combined treatment lost significantly (P < 0.02) more weight (5.2% ± 1.2%) than those assigned to CBT-D (0.8% ± 1.3%) and comparable amounts as those in BWC (3.5% ± 1.3%). Depression scores decreased significantly from baseline levels in each group, with no significant differences between groups. All three groups showed significant improvements in 10-year CVD risk, with no significant differences between groups. Groups did not differ significantly on any of these measures at week 46.BWC yielded short-term improvements in weight, mood, and CVD risk, comparable to a combined treatment that incorporated CBT-D. Results require replication with a larger sample size.