Introduction: The postoperative pain is one of the most important factors influencing fear and anxiety. The use of inhalation sedation makes a patient relax and pain-free during surgery. This study aimed to assess the effects of 50% nitrous oxide on postoperative pain after third molar teeth surgery. Materials and Method: Forty-three adult patients were involved in this prospective randomized controlled clinical trial. All patients were of ASA1 status. The subjects were divided randomly into two groups receiving 100% oxygen or 50% nitrous oxide/50% oxygen. The degree of the postoperative pain was assessed at different periods: 6 hours after the surgery, 12 hours after surgery, and 24 hours after surgery by VAS. The number of oral analgesic (Ibuprofen 400mg) taken during the first 24 hours was also assessed in the two groups. Data were analyzed with Chi-Square and Independent Sample T-test. Results: The pain score and the amount of total analgesic consumption in the nitrous oxide groups were significantly less than the oxygen group (P <0.005 respectively). The mean number of oral analgesics taken by the patients in the nitrous oxide and oxygen groups was 5.27 and 7.9 respectively. Conclusion: The admiration of nitrous oxide/oxygen mixture during third molar surgery can decrease postoperative pain.