Background and objective: The use of remifentanil requires other analgesics for postoperative pain relief compared to fentanyl in patients undergoing craniotomy. This could possibly reduce the postoperative advantages of this short-acting opioid. Methods: We compared remifentanil and fentanyl-based anaesthesia in a randomized observer and patient blinded trial on patients, undergoing an elective craniotomy. Twenty patients received anaesthesia using remifentanil with a small dose of piritramide (0.1 mg kg-1) after closure of the dura mater. Twenty patients underwent a fentanyl-based protocol. In both groups, anaesthesia was induced with thiopental and rocuronium, and maintained with 0.6-1 minimum alveolar concentration (MAC) isoflurane in a nitrous oxide/oxygen mixture 2:1 and rocuronium. Patients received 1 g of paracetamol rectally postoperatively. A visual analogue scale (VAS) for pain, the Glasgow Coma Score, a modified Aldrete Score, arterial carbon dioxide tension (PaCO2) and piritramide consumption were evaluated every half an hour postoperatively. Results: No significant differences were found for pain, Aldrete or Glasgow Coma scores or for PaCO2 between the groups when controlled for age, although the pain and Glasgow Coma Scores were consistently higher and PaCO2 lower in the remifentanil group. Furthermore, 13 out of 20 patients in the remifentanil group requested extra piritramide as opposed to 7 out of 20 in the fentanyl group (P = 0.11). Conclusions: Despite the intraoperative use of piritramide in the remifentanil group, patients experienced more pain postoperatively. A significant influence of age on pain intensity was found. The use of remifentanil with a small dose of piritramide of 0.1 mg kg-1 has no evident advantage over the use of fentanyl considering the postoperative conditions after craniotomy.