Background:To perform a meta-analysis to assess the efficiency and safety between local infiltration analgesia (LIA) and sciatic nerve block (SNB) when combined with femoral nerve block (FNB) for pain control following total knee arthroplasty (TKA).Methods:We systemically searched the following electronic databases for potentially relevant articles: Embase (1980–2017.01), Medline (1966–2017.01), PubMed (1966–2017.01), ScienceDirect (1985–2017.01), web of science (1950–2017.01) and the Cochrane Library. Only studies published in English that were accessible online were considered. Furthermore, we only considered studies that were published from 1966 to 2017. Only studies that met the following inclusion criteria were considered: (a) patients were adult human subjects who were set to undergo TKA; (b) the intervention was either SNB combined with FNB or LIA combined with FNB; (c) the outcomes of the studies, such as visual analog scale (VAS) scores, morphine consumption, length of stay and postoperative adverse effects, including the risk of nausea, vomiting and falls, were reported; (d) studies were either RCTs or non-RCT. Meta-analysis was performed using Stata 11.0 software. Modified Jadad score (7-points scale) which was based on Cochrane Handbook for Systematic Reviews of Interventions is used for assessment of RCTs. The Methodological Index for Nonrandomized Studies (MINORS) scale was used to assess non-RCTs with scores ranging 0 to 24. The synthesis of the outcomes for all studies was calculated as the weighted average rate by using a fixed or random effect model which depends on statistical heterogeneity. Systematic review registration number is CRD42017110661.Results:Three randomized controlled trials (RCTs) and 2 nonrandomized controlled trials (Non-RCTs), including 240 patients met the inclusion criteria. The present meta-analysis indicated that there were significant differences between groups in terms of visual analog scale (VAS) score at 12 hours (SMD = −0.337, 95% CI: −0.593 to −0.081, P =.010), VAS score at 24 hours (SMD = −0.337, 95% CI: −0.612 to −0.061, P =.017), morphine equivalent consumption at 24 hours (SMD = −0.371, 95% CI: −0.627 to −0.114, P = .005) and incidence of nausea (RD = 0.215, 95% CI: 0.078 to 0.353, P = .002) and vomiting (RD = 0.143, 95% CI: 0.026 to 0.260, P = .017).Conclusion:FNB combined with SNB provided decreased VAS scores and less morphine consumption at 12 and 24 hours compared with FNB combined with LIA in total knee arthroplasty. In addition, it was associated with lower risks of nausea and vomiting. We assessed the quality of the evidence as low to very low; therefore, our confidence in the effect estimate is limited, and the true effect may be substantially different from our estimates. Further studies should focus on surgeries that are known to be associated with significant postoperative pain, particularly surgeries where improved pain control may deliver significant clinical benefits through reduced morbidity, or cost-effectiveness benefits through faster r...