Abstract Overweight or obesity is an established negative prognostic factor in breast cancer. Co-morbidities associated with obesity, including cardiovascular disease (CVD), may negatively impact quality of life and survival in this population. Our purpose was to determine the effect of a cognitive behavioral therapy (CBT) intervention for weight loss through exercise and diet modification on risk factors for recurrence of breast cancer, and risks for CVD associated with obesity. Eighty-five overweight or obese breast cancer survivors were randomly assigned to a once weekly, 16-week intervention or wait-list control group. The intervention incorporated elements of CBT for obesity, addressing a reduction in energy intake, as well exercise, with a goal of an average of 1 h a day of moderate to vigorous activity. Body weight, total and regional body fat (by dual energy X-ray absorptiometry), waist and hip circumference, and blood lipids were assessed at baseline and following 16 weeks of intervention. Results: Seventy six women (89.4%) completed the intervention. Independent t-test to evaluate group differences at 16 weeks showed significant differences in weight, body mass index, percent fat, trunk fat, leg fat, as well as waist and hip circumference between intervention and control groups (P £ 0.05). Furthermore, levels of triglycerides and total cholesterol/high density lipoprotein cholesterol levels were also significantly reduced following the intervention. These results indicate that 16 weeks of a CBT program for weight management may reduce obesity and CVD risk in overweight breast cancer survivors.