The aim of this study was to compare the analgesic efficacy of three different postoperative treatments after supratentorial craniotomy. Sixty-four patients were allocated prospectively and randomly into three groups: paracetamol (the P group, n = 8), paracetamol and tramadol (the PT group, n = 29), and paracetamol and nalbuphine (the PN group, n = 27). General anesthesia was standardized with propofol and remifentanil using atracurium as the muscle relaxant. One hour before the end of surgery, all patients received 30 mg/kg propacetamol intravenously then 30 mg/kg every 6 hours. Patients in the PT group received 1.5 mg/kg tramadol 1 hour before the end of surgery. For patients in the PN group, 0.15 mg/kg nalbuphine was injected after discontinuation of remifentanil, because of its &mgr;-antagonist effect. Postoperative pain was assessed in the fully awake patient after extubation (hour 0) and at 1, 2, 4, 8, and 24 hours using a visual analog scale (VAS). Additional tramadol (1.5 mg/kg) or 0.15 mg/kg nalbuphine was administered when the VAS score was ≥ 30 mm. Analgesia was compared using the Mantha and Kaplan–Meier methods. Adverse effects of the drugs were also measured. The three groups were similar with respect to the total dose of remifentanil received (0.27 ± 0.1 &mgr;g/kg/min). In all patients, extubation was obtained within 6 ± 3 minutes after remifentanil administration. Postoperative analgesia was ineffective in the P group; therefore, inclusions in this group were stopped after the eighth patient. Postoperative analgesia was effective in the two remaining groups because VAS scores were similar, except at hour 1, when nalbuphine was more effective (P= .001). Nevertheless, acquiring such a result demanded significantly more tramadol than nalbuphine (P< .05). More cases of nausea and vomiting were observed in the PT group but the difference was not significant (P< .06). In conclusion, pain after supratentorial neurosurgery must be taken into account, and paracetamol alone is insufficient in bringing relief to the patient. Addition of either tramadol or nalbuphine to paracetamol seems necessary to achieve adequate analgesia, with, nevertheless, a larger dose of tramadol to fulfill this objective.