BACKGROUND: Postoperative pain after total knee arthroplasty (TKA) is intense and remains an unsolved problem. Some studies show that perioperative, multimodal analgesia, including intravenous dexamethasone, can provide a better analgesic effect; however, the validity of studies has raised concerns and questions remain around the efficacy, dosing, and safety of dexamethasone in patients undergoing total knee arthroplasty. OBJECTIVES: The purpose of this systematic review and meta-analysis was to evaluate the impact of intravenous dexamethasone on postoperative pain among patients undergoing TKA. STUDY DESIGN: Systematic review and meta-analysis. SETTING: Web of Science, Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched to identify relevant randomized controlled trials. The last search was in August 2021. METHODS: The risk of bias of the included trials was assessed by the Cochrane Risk of Bias Tool. The primary outcome was postoperative visual analog scale (VAS) pain scores and secondary outcomes included cumulative equivalent intravenous morphine consumption, number of patients requiring rescue analgesic, length of hospital stay, and adverse events. We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Eleven studies with 1,671 patients were included. The pooled results indicated that patients receiving dexamethasone had lower VAS pain scores at rest (24 h, MD = -0.68, [95% CI: -0.87 to -0.49]; 48 h, MD = -0.33, [95% CI: -0.46 to -0.21]) and at movement (24 h, MD = -0.74, [95% CI: -1.10 to -0.37]; 48 h, MD = -0.46, [95% CI: -0.66 to -0.26]), required less morphine (24 h, MD = -2.84 mg, [95% CI: -5.13 to -0.54]; 48 h, MD= -4.16 mg, [95% CI: -5.55 to -2.78]) and rescue analgesics, and had shorter hospitalization. There was no increase in infection, gastrointestinal hemorrhage, wound healing problems, or blood glucose levels with dexamethasone. Subgroup analysis did not observe difference between single dose and repeat dose groups. LIMITATIONS: The perioperative multimodal analgesia measures were varied throughout the studies. The sample size was small for some outcomes and high heterogeneity was observed. CONCLUSIONS: Our results supported the addition of perioperative intravenous dexamethasone to multimodal analgesia in total knee arthroplasty to reduce postoperative pain, opioids consumption, and length of hospital stay. Current evidence did not support the superiority of repeated-dose dexamethasone over single-dose dexamethasone; thus, we recommended perioperative 8-10 mg intravenous dexamethasone to be used based on adequate basic analgesia; however, the results may have been affected by small sample sizes and heterogeneity.