One hundred twenty-four patients with end-stage knee osteoarthritis undergoing primary unilateral total knee arthroplasty were randomized to receive either intravenous betamethasone sodium phosphate (10.52 mg; n=62) or normal saline placebo (n=62) 10 minutes before anesthesia induction. The primary outcome was severity of nausea, frequency of vomiting, and use of antiemetic medication within 48 hours postoperatively. Secondary outcomes included pain scores, knee range of motion, blood glucose, inflammatory markers (CRP, IL-6, ESR), and adverse reactions. Outcomes were assessed at multiple intervals up to 48 hours postoperatively. Overall, the results of the study revealed significantly lower nausea severity (P < 0.001), reduced vomiting at 2 hours (P < 0.001), and lower use of metoclopramide (P < 0.001) in the betamethasone group. Additionally, CRP and IL-6 levels were significantly reduced postoperatively. These findings suggest that prophylactic betamethasone is effective and safe for reducing PONV after TKA without affecting pain, glucose, or increasing adverse events.