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Molecular Adsorbent Recirculating System (MARS) is an artificial liver support system that has been developed for patients with liver failure until the liver regains function or as a bridge to transplantation. We conducted a meta-analysis to examine the efficacy of this promising therapy. We searched MEDLINE, EMBASE, and the Cochrane Registry of Controlled Trials databases, and abstracts from the proceedings of several scientific meetings. Patients with acute, acute on chronic, and hyperacute liver failure were included and we compared MARS with standard medical therapy. Randomized and nonrandomized controlled trials were included and Molecular Adsorbent Recirculating System was the intervention used. We evaluated net change in total bilirubin levels, improvement in hepatic encephalopathy and mortality. Nine randomized controlled trials and one nonrandomized controlled study met criteria and were included. By meta-analysis, MARS resulted in a significant decrease in total bilirubin levels (net change−7.0 mg/dl; 95% CI−10.4,−3.7; p < 0.001) and in an improvement in the West-Haven grade of hepatic encephalopathy (odds ratio [OR] 3.0; 95% CI 1.9, 5.0; p < 0.001). There was no beneficial effect on mortality (OR 0.91; 95% CI 0.64, 1.31; p = 0.62). The limitations of this study include a small sample size, an inability to blind with significant heterogeneity among studies, and variable definitions of liver failure. The Molecular Adsorbent Recirculating System is associated with a significant improvement in total bilirubin levels and hepatic encephalopathy but has no impact on survival. Large studies are required to assess the merit of this promising therapy on patient-centered outcomes.