BACKGROUND AND PURPOSE: The use of nucleoside antivirals and hepatitis B immunoglobulin (HBIG) is effective in preventing hepatitis B virus relapse after liver transplantation. Recently, it has been shown that the use of nucleoside antivirals alone is also effective in preventing hepatitis B recurrence after liver transplantation. This systematic study and meta-analysis was conducted to investigate the need for hepatitis B immunoglobulin in the context of the current use of new nucleoside analogues. METHODS: A meta-analysis was conducted on the use of hepatitis B immunoglobulin after liver transplantation. The databases searched included PubMed/MEDLINE, China Knowledge Network, and Wanfang database. The studies were focused on the recurrence rate of hepatitis B after liver transplantation, patient survival rate, hepatitis B virus mutation rate, etc. Results: Nine studies totaling 1484 were included in this analysis. The results showed that the use of hepatitis B immunoglobulin was effective in reducing the viral recurrence rate [P<0.001; RD=0.16; 95% confidence interval (CI) (0.12, 0.20)] and viral mutation rate [P<0.001; RR=3.13; 95% CI (1.86-5.26)], as well as in increasing the 1-year survival rate [P=0.03 ; RD=0.08; 95% CI (0.01, 0.15)] and 3-year survival [P=0.005; RD=0.17; 95% CI (0.05, 0.28)]. The 5-year survival rate of patients was not significantly different [P=0.46; RD=-0.06; 95% CI (-0.21, 0.10)]. Subgroup analysis showed that HBIG use reduced viral recurrence when patients were preoperatively HBV DNA-positive (P<0.001; RD=0.42; 95% CI (0.32, 0.52)) and did not significantly help when patients were preoperatively HBVDNA-negative (P=0.18; RD=0.06; 95% CI (-0.03, 0.14 )). HBIG use was also not significantly helpful when using next-generation nucleoside analogues (P=0.37; RD=0.06; 95% CI (-0.02, 0.14)). Conclusion: HBIG in combination with nucleoside analogues is effective in reducing viral recurrence and mutation rates. The need for HBIG when using novel nucleoside antivirals, especially when patients are postoperatively HBVDNA-negative, needs further study.