BACKGROUND Gastroesophageal reflux disease (GERD) is a common cause of morbidity and health-care utilization in many countries. Obesity is a potentially modifiable risk factor, but existing studies have conflicting results, possibly due to differences in study design, definitions, or populations. METHODS We performed a systematic review and meta-analysis of studies identified using MEDLINE, the Web of Science electronic database, manual literature review, and a review of expert bibliographies. Studies were included if they: (1) evaluated obesity, body mass index (BMI), or another measure of body size; (2) included data on reflux symptoms, esophagitis, or a GERD-related hospitalization; and (3) reported a relative risk or odds ratio (OR) with confidence intervals or provided sufficient data to permit their calculation. RESULTS We identified 20 studies that included 18,346 patients with GERD. Studies from the United States demonstrated an association between increasing BMI and the presence of GERD (95% confidence interval [CI]= 1.36–1.80, overweight, OR = 1.57, P value homogeneity = 0.51, 95% CI = 1.89–2.45, obese, OR = 2.15, P= 0.10). Studies from Europe provided heterogeneous results despite stratification for several factors; individual studies demonstrated both positive associations and no association. CONCLUSIONS This analysis demonstrates a positive association between increasing BMI and the presence of GERD within the United States; this relationship became apparent only after stratification by country and level of BMI. These results support the evaluation of weight reduction as a potential therapy for GERD. Further studies are needed to evaluate potential mechanisms and any differences in this relationship among different study populations.