Twenty-four gynaecological patients receiving postoperative patient-controlled analgesia were enrolled in an open cross-over pilot study evaluating two new formulations of nasal fentanyl spray. The primary outcome was the bioavailability of nasal fentanyl in comparison with intravenous fentanyl. This manuscript describes the clinical outcomes of quality of postoperative analgesia and patient acceptability. There were 21 complete data sets for both sequences of the cross-over design. In randomised order, patients received approximately 50 microg of fentanyl in a single dose by intranasal and intravenous administration, but separated by at least 2 h. Analgesia was of rapid onset (within 5 min) and similar quality. There was no significant difference in side-effects. Four patients experienced mild nasal stinging and although 10 (42%) preferred intravenous administration, seven (29%) preferred intranasal and six (25%) had no preference. We conclude that these formulations of fentanyl, delivered as nasal spray, have potential clinical utility.