OBJECTIVE: To investigate the preventive effect of antireflux surgery against esophageal adenocarcinoma (EAC) compared with medical treatment of gastroesophageal reflux disease (GERD) and to the background population. BACKGROUND: GERD is causally associated with EAC. Effective symptomatic treatment can be achieved with medication and antireflux surgery; however the possible preventive effect on EAC development remains unclear. METHODS: This systematic review identified 10 studies comparing EAC risk after antireflux surgery with nonoperated GERD patients, including 7 studies of patients with Barrett's esophagus, and 2 studies comparing EAC risk after antireflux surgery to the background population. A fixed-effects Poisson meta-analysis was conducted to calculate pooled incidence rate ratios (IRR) and 95% confidence intervals (CIs). RESULTS: The pooled IRR in patients after antireflux surgery was 0.76 (95% CI 0.42-1.39) compared with medically treated GERD patients. In patients with Barrett's esophagus, the corresponding IRR was 0.46 (95% CI 0.20-1.08), and 0.26 (95% CI 0.09-0.79) when restricted to publications after 2000. There was no difference in EAC risk between antireflux surgery and medical treatment in GERD patients without known Barrett's esophagus (IRR 0.98, 95% CI 0.72-1.33). The EAC risk remained elevated in patients after antireflux surgery compared with the background population (IRR 10.78, 95% CI 8.48-13.71). Although the clinical heterogeneity of the included studies was high, the statistical heterogeneity was low. CONCLUSIONS: Antireflux surgery may prevent EAC better than medical therapy in patients with Barrett's esophagus. The EAC risk after antireflux surgery does not seem to revert to that of the background population.