ObjectiveTo systematically review the diagnostic value of HBV Pre-S1Ag tested by enzyme-linked immunosorbent assay (ELISA) in patients with hepatitis B virus replication. MethodsSuch databases as PubMed, EMbase, The Cochrane Library (Issue 3, 2014), CBM, CNKI, VIP and WanFang Data were electronically and comprehensively searched for relevant studies on the diagnostic value of HBV Pre-S1Ag tested by ELISA in patients with hepatitis B virus replication from inception to May 1st, 2014. Relevant journals were also manually retrieved. Two reviewers independently screened literature according to inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Meta-analysis was then conducted using Meta-Disc 1.4 software. ResultsFinally, fifteen studies were included, involving 1 994 patients with hepatitis B diagnosed by the gold standard and 526 patients with non-hepatitis B diseases. The results of meta-analysis showed (Sen=0.76, 95%CI 0.74 to 0.78; Spe=0.90, 95%CI 0.88 to 0.91; +LR=8.54, 95%CI 4.25 to 17.15;-LR=0.17, 95%CI 0.10 to 0.27; DOR=65.12, 95%CI 24.91 to 170.28; AUC=0.943 0, SE=0.018 1; Q*=0.881 3, SE=0.023 4). ConclusionHBV Pre-S1Ag tested by ELISA has certain value in the diagnosis of patients with hepatitis B virus replication. Due to poor methodological quality of the included studies, the above conclusion should be verified by conducting high quality diagnostic tests.