One hundred fifty patients undergoing unilateral primary total knee arthroplasty for knee osteoarthritis were randomized to receive either placebo (Group A, n=50), a single 10 mg dose of dexamethasone preoperatively (Group B, n=50), or two 5 mg doses of dexamethasone pre- and postoperatively (Group C, n=50). The primary outcome was the incidence and severity of postoperative nausea and vomiting (PONV) within 24 hours post-surgery. Secondary outcomes included consumption of morphine and metoclopramide, visual analog scale (VAS) scores for PONV at 2, 4, 6, and 24 hours, postoperative blood glucose levels (days 1–3), and complications such as surgical site infection (SSI) and gastrointestinal bleeding (GIB) within 45 days. Overall, the results revealed that both dexamethasone groups had significantly reduced PONV, rescue medication use, and VAS scores compared to placebo, with the two-dose group (Group C) outperforming the single-dose group (Group B). Dexamethasone had no significant impact on blood glucose or complication rates. These findings suggest that two-dose dexamethasone is more effective than a single dose in reducing early PONV without increasing complications.