BACKGROUND: Exposure to acid and duodeno-gastro-oesophageal reflux (DGOR) both increase with oesophageal lesions in gastro-oesophageal reflux disease (GORD). It is unknown whether DGOR exposure is an independent risk factor for oesophageal lesions. A multivariate analysis was performed on the relationship between oesophageal lesions and demographics and acid and DGOR exposure. METHODS: In 422 patients with suspected GORD, upper endoscopy, oesophageal manometry, and pH and DGOR monitoring were performed. Stepwise logistic regression was used to identify factors associated with the presence of oesophagitis, severity of oesophagitis and the presence of Barrett's oesophagus. ORs and 95% CIs were computed at different cut-offs. RESULTS: 54% of the patients had no oesophagitis, 36% had grade A-B oesophagitis, 3% had grade C-D oesophagitis and 7% had Barrett's oesophagus. In multivariate analysis, oesophagitis was associated with hiatal hernia (OR 3.621, 95% CI 2.263 to 5.794) and DGOR exposure (OR up to 2.236, 95% CI 1.356-3.685), while a low body mass index (BMI) seemed protective (OR for BMI >first quartile 2.245, 95% CI 1.371 to 3.677). Severity of oesophagitis was only associated with acid exposure (OR up to 5.038, 95% CI 1.452 to 17.480). The presence of Barrett's oesophagus was associated with male sex (OR 3.621, 95% CI 2.263 to 5.794), DGOR (OR up to 5.017, 95% CI 2.051 to 12.274) and acid exposure (OR up to 3.031, 95% CI 1.216 to 7.556). CONCLUSIONS: Several independent factors are associated with oesophageal lesions in GORD. The risk of oesophagitis is associated with hiatal hernia, BMI and DGOR exposure; severity of oesophagitis depends on acid exposure; and Barrett's oesophagus is associated with male sex and exposure to both acid and DGOR.