OBJECTIVE: To evaluate how antireflux surgery influences the risk of esophageal cancer in patients with gastroesophageal reflux disease (GERD) and Barrett esophagus. BACKGROUND: GERD is a major risk factor for esophageal adenocarcinoma, and the United Kingdom has the highest incidence of esophageal adenocarcinoma globally. METHODS: Hospital Episode Statistics database was used to identify all patients in England aged over 18 years diagnosed with GERD with or without Barrett Esophagus from 2000 to 2012, with antireflux surgery being the exposure investigated. The Clinical Practice Research Datalink (CPRD) was used to provide a sensitivity analysis comparing proton pump inhibitor therapy and antireflux surgery. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards model with inverse probability weights based on the probability of having surgery to adjust for selection bias and confounding factors. RESULTS: (i) Hospital Episode Statistics analysis; among 838,755 included patients with GERD and 28,372 with Barrett esophagus, 22,231 and 737 underwent antireflux surgery, respectively. In GERD patients, antireflux surgery reduced the risk of esophageal cancer (HR = 0.64; 95% CI 0.52-0.78). In Barrett esophagus patients, the corresponding HR was (HR = 0.47; 95% CI 0.12-1.90).(ii) CPRD analysis; antireflux surgery was associated with decreased point estimates of esophageal adenocarcinoma in patients with GERD (0% vs. 0.2%; P = 0.16) and Barrett esophagus (HR = 0.75; 95% CI 0.21-2.63), but these were not statistically significant. CONCLUSION: Antireflux surgery may be associated with a reduced risk of esophageal cancer risk, however it remains primarily an operation for symptomatic relief.