This prospective, double-blind, randomized, and placebo-controlled trial was performed to evaluate the effect of preincisional scalp infiltration with 0.25% bupivacaine on the postoperative pain perception and analgesic requirement of patients undergoing elective supratentorial craniotomy. Twenty patients (bupivacaine group) received scalp infiltration with 25 mL of 0.25% bupivacaine followed by intravenous 5 mL of saline as placebo 5 minutes before incision, and another 21 patients (fentanyl group) received scalp infiltration with a similar volume of 0.9% saline solution followed by 2 microg/kg of intravenous fentanyl 5 minutes before incision. Following standard anesthesia technique, basal, preincisional, and postincisional hemodynamic data were recorded. Postoperative pain was assessed at 1, 6, 12, 24, and 48 hours by using a 10-cm visual analog scale. Diclofenac sodium was used as rescue analgesic in the postoperative period. Results showed rescue analgesic was required only during the first 12 hours. In each group the same number of patients needed rescue analgesia, but bupivacaine delayed this requirement 105 (30-720; median [range]) minutes compared with 60 (15-720; median [range]) minutes for the fentanyl group (P = 0.13). But there was no difference in the amount of analgesic consumed at different time intervals. Six of 20 patients in the bupivacaine group required rescue analgesic at the end of 1 hour compared with 9 of 21 fentanyl patients (P = 0.61). At 6 hours, the fraction of patients who required rescue analgesia were 7 of 20 and 11 of 21, respectively (P = 0.44). In conclusion, bupivacaine preincision scalp infiltration did not have any significant effect on postcraniotomy pain and analgesic requirement. However, bupivacaine may delay the requirement of the first analgesic dose.