Objective To evaluate the effectiveness of combination therapy with lamivudine (LAM) and hepatitis B immunoglobulin (HBIG) versus LAM monotherapy in prevention of hepatitis B virus recurrence after liver transplantation. Methods Databases including MEDLINE (Ovid), PubMed, EMbase, Cochrane Central Register of Controlled Trials (CENTRAL), CBM, VIP, and CNKI were searched up to Dec. 2008. Clinical trials including randomized controlled, non-randomized concurrent-control and case-control studies about combination therapy with HBIG and LAM versus LAM monotherapy in prevention of hepatitis B virus recurrence after liver transplantation were screened. Trial selection and data extraction were conducted by two reviewers independently. Meta-analysis was performed using RevMan 5.0.18 software. Results Eleven non-randomized concurrent-control studies involving 1 421 patients (1 035 patients in combination therapy group, and 386 patients in LAM monotherapy group) were included. The results of meta-analyses showed: Compared with LAM monotherapy group, the risks of hepatitis B virus recurrence, YMDD mutation, and death associated with HBV recurrence were significantly reduced by 73% (RR=0.27, 95%CI 0.20 to 0.37, Plt;0.000 01), 72% (RR=0.28, 95%CI 0.15 to 0.53, P=0.000 01), and 79% (RR=0.21, 95%CI 0.09 to 0.49, P=0.000 3) respectively in combination therapy group after liver transplantation; overall survival rates of both recipients and grafts in combination therapy group were similar to LAM monotherapy group (RR=1.03, 95%CI 0.95 to 1.11, P=0.51; RR=1.04, 95%CI 0.97 to 1.12, P=0.26). Conclusion Current evidence indicates that compared with LAM monotherapy, combination therapy with LAM and HBIG could reduce the risks of hepatitis B virus recurrence, YMDD mutation, and death associated with HBV recurrence after liver transplantation.