BACKGROUND: This meta-analysis aimed to perform a meta-analysis to evaluate the efficiency and safety between local infiltration analgesia (LIA) and sciatic nerve block (SNB) when combined with femoral nerve block (FNB) after total knee arthroplasty (TKA). METHODS: A systematic search was performed in MEDLINE (1966-2017.04), PubMed (1966-2017.04), Embase (1980-2017.04), ScienceDirect (1985-2017.04), and the Cochrane Library. Only high-quality studies were selected. Meta-analysis was performed using Stata 11.0 software. RESULTS: Four randomized controlled trials (RCTs) and two non-randomized controlled trials (non-RCTs), including 273 patients met the inclusion criteria. The present meta-analysis indicated that there were significant differences between groups in terms of visual analogue scale (VAS) score at 12 h (SMD = -0.303, 95% CI -0.543 to -0.064, P = 0.013), VAS score at 24 h (SMD = -0.395, 95% CI -0.636 to -0.154, P = 0.001), morphine equivalent consumption at 24 h (SMD = -0.395, 95% CI -0.636 to -0.154, P = 0.001), and incidence of nausea (RD = 0.233, 95% CI 0.107 to 0.360, P = 0.000) and vomiting (RD = 0.131, 95% CI 0.025 to 0.237, P = 0.015). CONCLUSION: FNB-combined SNB provides superior pain relief and less morphine consumption within the first 24 h compared FNB-combined LIA in total knee arthroplasty. In addition, there were fewer side effects associated with SNB. Because the sample size and the number of included studies were limited, a multicenter RCT is needed to identify the effects of the two kinds of methods and further work must include range of motion analyses and functional test.