Background Obesity and overweight have been positively related to gastro-oesophageal reflux disease (GERD). It has been suggested that this relationship is as a consequence of an increased gastric acid reflux, which is caused by an enhanced intra-abdominal pressure. Aim To assess potential interaction of the association between body mass index (BMI) and GERD by chronic atrophic gastritis, which goes along with decreased acid production. Methods In the baseline examination of ESTHER, a study conducted in 9953 older adults in Saarland, information on frequency of heartburn, potential risk factors and medical history was obtained by self-administered standardized questionnaire. Serological measurements of pepsinogen I and II were taken for definition of chronic atrophic gastritis. Results In total, 2565 (28.7%) of the included subjects experienced heartburn within the previous 4 weeks. A pronounced dose-response relationship was observed between BMI and heartburn occurrence (P < 0.001) among people without chronic atrophic gastritis, but not among people with chronic atrophic gastritis (P-value for interaction = 0.018). Obese/overweight people with chronic atrophic gastritis had a much lower risk of heartburn compared with obese/overweight people without chronic atrophic gastritis (OR = 0.31, 95% CI = 0.24-0.40). Conclusion Our results are consistent with the hypothesis that BMI is related positively to GERD symptoms by its impact on acid reflux. © 2010 Blackwell Publishing Ltd.