As evidence-based strategies to the clinical management of Barrett's esophagus (BE) are lacking, we have carried out a systematic review and meta-analysis of all published randomized controlled trials with the aim of evaluating the value of different approaches in the treatment of BE. Searches were conducted in the databases PUBMED, EMBASE, and Cochrane Library. Thirteen randomized clinical trials that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were assessed in more detail. Based on our search, neither the pharmacological nor surgical therapies currently available for reflux appear to achieve complete regression of BE and the elimination of the cancer risk associated with it. In contrast, endoscopic ablative techniques are capable of achieving endoscopic and histological reversal of BE, with ablation by argon plasma coagulation (APC) appearing to be more effective than treatment with photodynamic therapy (PDT) [odds ratio (OR) 3.46, 95% confidence interval (CI) 1.67-7.81, P = 0.0008]. There was no statistically significant difference between APC and multipolar electrocoagulation (MPEC) in terms of the efficacy to achieve regression of BE (OR 2.01, 95% CI 0.77-5.23, P = 0.15). In conclusion, there have been only a limited number of randomized controlled trials that compare treatments for BE. The pharmacological therapy, antireflux surgery, and endoscopic ablative techniques are promising in terms of treating BE, but the studies carried out to date have had no adequate power to assess the effect of treatment on reducing and preventing progression to adenocarcinoma.