Objective:To investigate the efficacy and safety of the second generation argon plasma coagulation(VIO APC) in the ablation of Barrett’s Esophagus. Methods:A total of 35 patients with uncomplicated Barrett’s esophagus entered into a prospective, randomized, unblinded study comparing the treatment VIO APC combined with a proton pump inhibiter with a proton pump inhibiter administered alone. VIO APC was performed at a power setting of 40W, and argon gas flow at 1.5-2.0 L/min, and“forced”mode. Ablative treatment was repeated until either no Barrett’s epithelium remained or a maximum of 5 treatment sessions occurred. Results:In the ablation group, macroscopic complete ablation was achieved in 14 of 18 patients, and complete ablation confirmed by histology in 12 of 18 patients(P < 0.01). Buried glands were observed in 2 patients who had achieved macroscopic ablation. The Barrett’s mucosa averaged a reduction of 65%(range 50-75%) in the remaining 4 patients. In the control group, only 2 patients had partial regression, median 30%(range 20-40%). In the ablation group, post-treatment 4 patients had transient retrosternal pain, and 3 patients had mild epigastric discomfort. One patient had a small hemorrhage during the procedure, which ceased after norepinephrine and thrombosin were administered through the endoscope biopsy channel. No adverse events were observed in the control group. During 11.8(4-15) months follow-up, patients who had achieved the complete ablation have no evidence of relapse of Barrett’s esophagus. Conclusion:VIO APC with a relatively low power setting can effectively ablate the Barrett’s mucosa. No severe adverse events were observed. Long-term follow-up is needed to assess cancer prevention and the durability of the neo-squamous epithelium.