BACKGROUND: This meta-analysis aimed to evaluate the efficiency and safety of the combined adductor canal block with peri-articular infiltration versus periarticular infiltration alone for pain control after total knee arthroplasty (TKA). METHODS: PubMed, Medline, Embase, Web of Science, and the Cochrane Library were searched to identify articles comparing the combined adductor canal block with peri-articular infiltration and periarticular infiltration alone for pain control after TKA. Main outcomes were numeric rating scale (NRS) at postoperative day (POD) 0-2 and opioid consumption. Meta-analysis was performed using Stata 11.0 software. RESULTS: Four randomized controlled trial (RCTs) including 297 patients met the inclusion criteria. The present meta-analysis indicated that there were significant differences between the groups regarding NRS score at POD 0 (weighted mean difference [WMD] = -0.849, 95% confidence interval [CI]: -1.345 to -0.353, P = .001), POD 1 (WMD = -0.960, 95% CI: -1.474 to -0.446, P = .000), and POD 2 (WMD = -0.672, 95% CI: -1.163 to -0.181, P = .007) after TKA. Significant differences were found in terms of opioid consumption at POD 0 (WMD = -3.761, 95% CI: -6.192 to -1.329, P = .002), POD 1 (WMD = -4.795, 95% CI: -8.181 to -1.409, P = .006), and POD 2 (WMD = -2.867, 95% CI: -4.907 to -0.827, P = .006). CONCLUSION: Combined adductor canal block with peri-articular infiltration could significantly reduce NRS scores and opioid consumption in comparison with periarticular infiltration alone following TKA. Additionally, there is a lower incidence of nausea and vomiting in the combined groups.