【Objective】To investigate the best time for the patients with HBV acute-on-chronic liver failure to undergo allogeneic bone marrow mesenchymal stem cells transplantation. 【Methods】 A total of 91 inpatients with HBV related acute on chronic liver failure (HBV-ACLF) were recruited and randomized into two groups: MSC-treatment group (n = 45) and control group (n = 46). 45 patients who received bone marrow mesenchymal stem cells (BM-MSC) transplantation were divided into two subgroups: MSC-advanced group (n = 12) and MSC-plateau (n = 33); 46 patients as control group received standard medical treatment were divided into two subgroups: Control-advanced (n = 13) and Control-plateau (n = 33). Primary endpoint include 12 weeks cumulative survival rate in different treatment phase of MSC groups and control groups

and the secondary endpoints are changes of MELD scores and serum total bilirubin in different groups and subgroups. 【Results】 The 12-week cumulative survival rate of the patients was slightly increased in MSC-advanced group (6/12

50%)

but not significantly different than that in control-advanced group (6/13

46.2%) (P = 0.202). And the 12-week cumulative survival rate of patients in MSC-plateau group (28/33

84.8%) was much higher than that of patients in control-plateau group (18/33

52.2%) (P = 0.0037). Within the MSC treatment groups

the 12-week cumulative survival rate in MSC-plateau group (84.8%

28/33) was greater than that of MSC-advanced group (50%

6/12) (P = 0.009). Serum total bilirubin levels of patients in the MSC-plateau group improved from baseline in 2

4 weeks were (-97 ± 124)μmol/L

(-189 ± 166)μmol/L while there were (10 ± 206)μmol/L

(-10 ± 275)μmol/L in MSC-advanced group. MELD scores of patients in the MSC-plateau group improved from baseline in 4 and 12 weeks were (-3.8 ± 4.5) and (-12.5 ± 5.1) while there were (3.8 ± 8.1) and (-4.7±5.3) in MSC-advanced group. 【Conclusion】 Operating allogeneic peripheral BM-MSC transplantation in the plateau patients with HBV-ACLF can improve survival rate of the patients.