Background : The worldwide shortage of donor livers has prompted the search for alternative cell therapies for patients suffering from end-stage liver disease, including the transplantation of stem cells. Methods : We report ninety liver cirrhosis patients randomized to receive either a single session (group I) or two sessions, 4 months apart (group II) of autologous HSCs transplantation and a control group (group III). G-CSF was administered to transplanted patients before infusion. HSCs were isolated by bone marrow aspiration. CD34+ and CD 133+ cells were isolated and infused locally in the portal vein and systemically in a peripheral vein for one session in group I and two sessions in group II. After stem cell therapy, liver function was monitored for 12 months. Results : There was statistically significant improvement in the transplanted patients as regards mean serum albumin and non-significant improvement as regards bilirubin levels and INR which started to improve after 2 weeks of the procedure and continued to improve till the 6th month in the single infusion group but continued throughout the follow-up period in the repeated infusion group. By the end of the study, 36.7% of patients in group I and 66.7% in group II showed improvement in the degree of ascites with none of the infused patients showing deterioration of the degree of ascites. There was improvement in the hepatic functional reserve as assessed by the Child-Pugh and MELD score. Safety of the procedure was evidenced by low incidence of complications encountered.Conclusions : Using combined routes of HSCs infusion (peripheral veins and portal vein) in patients with end-stage liver disease has a beneficial effect on liver function with minimal adverse events with more lasting clinical efficacy after repeated HSCs infusion.