Introduction: Postoperative nausea and vomiting (PONV) is a frequent and clinically significant complication of surgery and anesthesia. The main objective of this study was to evaluate, in a double-blind and randomized manner, the efficacy of Ondansetron hydrochloride administered in intravenous patient control analgesia with Fentanyl for the prophylaxis of PONV in patients undergoing total hip replacement or total knee replacement procedures. Materials and Methods: Eighty-four Patients undergoing elective and primary total hip or total knee replacements were selected. After surgery, patients divided into 2 groups: in treatment group (n=42), patients received 0.16 mg/ml Ondansetron hydrochloride in Patient Controlled Analgesia IV (PCA/IV) pump with 5 µg/ml Fentanyl in 72 ml 0.9% isotonic sodium chloride and in control group (n=42), patients received PCA/IV pump with 5 µg/ml Fentanyl in 80 ml 0.9% isotonic sodium chloride. Then, patients were assessed for the presence and severity of nausea or vomiting and emetic episodes. Results: In control group, the incidence and severity of nausea as well as the incidence of vomiting and the severity of vomiting were greater compared to treatment group. Conclusion: The results indicate that Ondansetron provides superior control of PONV in patients undergoing total hip or knee replacement procedures.