ObjectiveTo systematically review the efficacy and safety of autologous mononuclear cells transplantation in osteonecrosis of the femoral head.MethodsPubMed, EMbase and The Cochrane Library were electronically searched to collect randomized and non-randomized controlled trials on autologous mononuclear cells transplantation for osteonecrosis of the femoral head from inception to July 31th, 2020. Two reviewers independently screened literatures, extracted data and assessed risk of bias of included studies. Meta-analysis was then performed using RevMan 5.4 software.ResultsA total of 17 studies involving 645 hips in mononuclear cells group and 557 hips in cell-free group were included. The results of meta-analysis showed that compared with cell-free therapy, mononuclear cells therapy could improve hip function in term of Hairrs score (MD=8.11, 95%CI 4.36 to 11.87, P<0.000 1), Merle D`Aubigné Postel score (MD=2.23, 95%CI 0.97 to 3.49, P=0.000 5), WOMAC score (MD=−10.81, 95%CI −15.80 to −5.81, P<0.000 1), Lequesne index (MD=−2.97, 95%CI −5.42 to −0.52, P=0.02) and alleviate the pain (MD=−9.13, 95%CI −12.40 to −5.86, P<0.000 01), delay the progression of radiological staging (RR=0.55, 95%CI 0.34 to 0.89, P=0.01) and reduce the rate of total hip arthroplasty (RR=0.61, 95%CI 0.43 to 0.86, P=0.005). In terms of safety, mononuclear cell therapy did not increase the rate of complications (RR=0.77, 95%CI 0.33 to 1.83, P=0.56).ConclusionsThe current evidence shows that autologous mononuclear cells therapy is a safe and effective way for osteonecrosis of the femoral head. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.