An increasing number of individuals undergo total knee arthroplasty (TKA), which can result in pain, limited motor function and adverse complications such as infection, nausea and vomiting. Glucocorticoids have been shown anti-inflammatory and antiemetic effects, but can also elevate blood glucose levels and increase the risk of wound infection. Thus, it is essential to investigate the efficacy and safety of glucocorticoid usage in TKA.A comprehensive systematic search of PubMed, Medline, EMBASE, Cochrane databases, to identify relevant randomized controlled trials (RCTs) of glucocorticoid application in TKA. The primary outcomes assessed were the postoperative pain assessment. Secondary outcomes included the range of motion in knee joint, levels of inflammatory cytokines, adverse complications, and the length of hospital stay.Thirty-six randomized controlled trials were included in the final analysis. The glucocorticoid group exhibited significant reduction in the resting VAS scores on postoperative days 1, 2 (POD1, 2)and postoperative 3 months (POM3), as well as decreased morphine consumption on POD1 and increased range of motion (ROM) in knee joint on POD1, 3. Additionally, the glucocorticoid group exhibited decreased levels of postoperative inflammatory cytokines and the incidence of PONV along with a shorter length of hospital stay. The blood glucose concentration was significantly increased in the glucocorticoid group on POD1 compared with the control group. While the blood glucose on POD2 and occurrence of postoperative adverse complications were similar between two groups including wound infection and venous thrombosis. The periarticular injection analgesia (PIA) group demonstrated lower VAS scores on POD2 comparing to the systemic administration (SA) group according to two studies. However, there was no significant difference of the resting VAS on POD1 and POD2 between PIA and SA group across all studies.Perioperative glucocorticoids treatment in TKA significantly reduced short-term pain score and opioid-use which was probably not patient relevant. The application of glucocorticoids in TKA implied a beneficial trend in analgesic, anti-inflammatory, and antiemetic effects, as well as improved range of motion and shortened hospital stay. While it will not increase the risk of continued high glucose, postoperative wound infection and venous thrombosis.© 2024. The Author(s).