AIM:To examine the effects of long-term proton pump inhibitor (PPI) therapy on body weight (BW) and body mass index (BMI) in patients with gastroesophageal reflux disease (GERD). METHODS:The subjects were 52 patients with GERD and 58 sex-and age-matched healthy controls. GERD patients were treated with PPI for a mean of 2.2 years (range, 0.8-5.7 years), and also advised on lifestyle modifications (e.g. selective diet, weight management). BW, BMI and other parameters were measured at baseline and end of study. RESULTS:Twenty-four GERD patients were treated daily with 10 mg omeprazole, 12 with 20 mg omeprazole, 8 with 10 mg rabeprazole, 5 with 15 mg lansoprazole, and 3 patients with 30 mg lansoprazole. At baseline, there were no differences in BW and BMI between reflux patients and controls. Patients with GERD showed increases in BW (baseline: 56.4 ± 10.4 kg, end: 58.6 ± 10.8 kg, mean ± SD, P < 0.0001) and BMI (baseline:23.1 ± 3.1 kg/m 2 , end: 24.0 ± 3.1 kg/m 2 , P < 0.001), but no such changes were noted in the control group. Mean BW increased by 3.5 kg (6.2% of baseline) in 37 (71%) reflux patients but decreased in only 6 (12%) patients during treatment. CONCLUSION:Long-term PPI treatment was associated with BW gain in patients with GERD. Reflux patients receiving PPI should be encouraged to manage BW through lifestyle modifications.