Objective: Weight gain is an important risk factor for gastroesophageal reflux disease (GERD); however, whether weight loss can lead to resolution of GERD symptoms is not clear. Our aim was to measure the impact of weight loss on GERD symptoms. Design and Methods: In a prospective cohort study at a tertiary referral center, overweight/obese subjects (BMI 25-39.9 kg/m2) were enrolled in a structured weight loss program.Weight loss strategies included dietary modifications, increased physical activity and behavioral changes. At baseline and at 6 months, BMI and waist circumference were measured and all participants completed a validated reflux disease questionnaire. Results: A total of 332 adult subjects, mean age 46 years and 66% women were prospectively enrolled. At baseline, the mean body weight, BMI, and waist circumference were 101 (618) kg, 35 (65) kg/m2 and 103 (613) cm. At 6 months, majority of the subjects (97%) lost weight (average weight loss: 13 6 7.7 kg) and as compared with baseline, there was a significant decrease in the overall prevalence of GERD (15 vs. 37%; P < 0.01) and the mean GERD symptom score (1.8 vs. 5.5; P < 0.01). Overall, 81% of the subjects had reduction in GERD symptom scores; 65% had complete resolution and 15% had partial resolution of reflux symptoms. There was a significant correlation between % body weight loss and reduction in GERD symptom scores (r = 0.17, P < 0.05). Conclusions: In conclusion, the overall prevalence of GERD symptoms is high (37%) in overweight and obese subjects. A structured weight loss program can lead to complete resolution of GERD symptoms in the majority of these subjects.