BACKGROUND & AIMS: Barrett's esophagus (BE) is a precursor lesion for esophageal adenocarcinoma (EAC). Surveillance endoscopy aims to detect early malignant progression; although widely practiced, it has not previously been tested in a randomized trial. METHODS: BOSS (Barrett's Oesophagus Surveillance Versus Endoscopy at Need Study) was a randomized controlled trial at 109 centers in the United Kingdom. Patients with BE were randomized to 2-yearly surveillance endoscopy or "at-need" endoscopy, offered for symptoms only. Follow-up was a minimum of 10 years. The primary outcome was overall survival in the intention-to-treat population. Secondary outcomes included cancer-specific survival, time to diagnosis of EAC, stage of EAC at diagnosis, frequency of endoscopy, and serious adverse events related to interventions. RESULTS: There were 3453 patients recruited; 1733 patients were randomized to surveillance and 1719 to at-need endoscopy. Median follow-up time was 12.8 years for the primary outcome. There was no evidence of a difference in overall survival between the surveillance arm (333 deaths among 1733 patients) and the at-need arm (356 deaths among 1719 patients; hazard ratio, 0.95; 95% CI, 0.82-1.10; stratified log-rank P = .503). There was no evidence of a difference for surveillance vs at-need endoscopy in cancer-specific survival (108 vs 106 deaths from any cancer; hazard ratio, 1.01; 95% CI, 0.77-1.33; P = .926), time to diagnosis of EAC (40 vs 31 patients had a diagnosis of EAC; hazard ratio, 1.32; 95% CI, 0.82-2.11; P = .254), or cancer stage at diagnosis. Eight surveillance patients (0.46%) and 7 at-need patients (0.41%) reported serious adverse events. CONCLUSIONS: Surveillance did not improve overall survival or cancer-specific survival. At-need endoscopy may be a safe alternative for low-risk patients. (ClinicalTrials.gov, Number: NCT00987857.).