Purpose: There has been great interest in recent years to take advantage of bone marrow stem cells to treat cirrhosis. Our uncontrolled trial showed promising results for bone marrow mesenchymal stem cell (MSC) transplantation in cirrhosis. We conducted a randomized, placebo-controlled trial to evaluate the efficacy of autologous MSC transplantation in cirrhosis. Methods: The enrolled patients with decompensated cirrhosis were randomly assigned to receive MSC or placebo infusions. A median of 245 million (range: 190 to 295 million) cultured MSCs were infused through a peripheral vein. The primary outcomes were absolute changes in MELD score, Child score, liver function tests, and liver volumes between the MSC and placebo group 12 months after infusion. Results: A total of 27 patients were enrolled. Of these, 15 patients received MSC and 12 patients received placebo. One patient in the MSC group and one patient in the placebo group were lost to follow-up. Three patients in the MSC group died of liver failure 3 months (1 patient), or 5 months (2 patients) after cellular infusion. The baseline MELD scores of the deceased patients were significantly higher than those who remained alive in either group (20.0 vs. 15.1; P: 0.02). Final analyses were performed in the remaining 22 patients (11 patients in each group) who completed 12 months of follow-up. The absolute changes in Child scores, MELD scores, serum albumin, INR, serum transaminases, and liver volumes did not differ significantly between the MSC and placebo groups at 12 months of follow-up. Five (45%) patients in the MSC group and 5 (45%) in the placebo group had improvement in MELD by 1 to 6 points at month 12 compared to baseline. Conclusion: This randomized, placebo-controlled trial showed no benefit of autologous bone marrow MSC transplantation through peripheral vein in cirrhotic patients. The observed improvements in MELD scores in 45% of the patients in MSC or placebo groups in the span of one year might be related to the natural course of cirrhosis or to the better supportive cares from the patients during the study period.Table: Mean of quantitative variables at baseline and 12 months after treatment