Medical costs of obesity in the United States exceed $147 billion annually with medication costs making a sizable contribution. We examined medication costs associated with substantial weight losses in an intensive behavioral weight loss program. Inclusion criteria were medication use for obesity co-morbidities: hypertension, diabetes, dyslipidemia, degenerative joint disease, or gastroesophageal reflux disease. Group A, 83 obese patients on medications completed 8 weeks of classes, lost 19 kg in 20 weeks. Group B, 100 severely obese patients, lost 59 kg in 45 weeks. Medications were discontinued: Group A, 18a7percnt;; Group B, 64%. Mean numbers of medications decreased significantly for all co-morbidities. Mean numbers of daily medications, initial and final, respectively were: Group A, total, 3.0 ± 0.2 (mean ± SEM) and 1.7 ± 0.2; Group B, total, 2.5 ± 0.2 and 0.7 ± 0.1. Monthly costs for all medications decreased significantly for all co-morbidities and were as follows: Group A, total, $249 ± 25 and $153 ± 19; Group B: total, 237 ± 27 and $65 12. Medically supervised weight loss is very effective approach for improving cardiovascular risk factors and reducing medical costs.