The comparison of Mesohepatectomy (MH) with conventional extended hemihepatectomies (EH) for patients with centrally located liver tumors (CLLTs) were inconsistent. Our aims were to systemically compare MH with EH and to determine whether MH can achieve a similar clinical outcome as EH through this meta-analysis. PubMed/Medline, EMBASE, Web of Knowledge and Cochrane Library were searched updated to June 11, 2016. Blood loss and operation time favored MH in elder patients (mean difference [MD] for blood loss: -692.82 ml, 95% CI: -976.72 to -408.92 ml, P < 0.001; MD for operation time: -78.75 min, 95% CI: -107.66 to -49.81, P < 0.001). Morbidity rate (29.2%, 95% CI: 24.1 to 34.8%), mortality rate (2.0%, 95% CI: 1.2 to 3.3%) and overall survival (median OS 38.2 m, 95% CI: 34.0 to 42.8 m) of MH were comparable with those of EH. The low liver failure rate favored MH (odds ratio [OR]: 0.29, 95% CI: 0.09 to 0.88, P = 0.03). For MH, bile leakage was the most common surgical complication (MH vs. EH: 13.5% vs. 6.7%, P = 0.016), while for EH, it was wound infection (MH vs. EH: 6.9% vs. 15.7%, P < 0.001). Thus MH might be in general safe and feasible for treating CLLTs with a similar clinical outcome as EH.