The prevalence of obesity has reached epidemic proportions. The treatment of obesity-related health conditions is costly. Although laparoscopic gastric bypass is expensive, health care costs in obese patients should decrease with subsequent weight loss and overall improved health. Specifically, monthly prescription medication costs should decrease quickly after surgery. Fifty consecutive laparoscopic gastric bypass patients at a university-based bariatric surgery program were enrolled in the study. Medication consumption was prospectively recorded in a database. Patients' monthly prescription (not over-the-counter) medication costs before surgery and 6 months postoperatively were calculated. Retail costs were determined by a query to drugstore.com, an online pharmacy. Generic drugs were selected when appropriate. Costs for diabetic supplies and monitoring were not included in this analysis. Patients were mostly female (86%). Mean body mass index preoperatively was 51 kg/m2. Mean excess weight loss at 6 months was 52%. Patients took an average of 3.7 prescription medications before surgery compared with 1.7 after surgery (P < 0.05). All patients took nonprescription nutritional supplements, including multivitamins, oral vitamin B12, and calcium postoperatively. Laparoscopic gastric bypass resulted in a significant improvement in comorbid health conditions as early as 6 months after surgery. In an unselected group of patients, this led to a substantial overall mean monthly prescription medication cost savings, especially in those with gastroesophageal reflux disease, hypertension, diabetes, and hypercholesterolemia.