We have evaluated the efficacy of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive constituent of cannabis, in postoperative pain. In a randomized double-blind, placebo-controlled, single-dose trial, we investigated 40 women undergoing elective abdominal hysterectomy. Randomization took place when postoperative patient-controlled analgesia was discontinued on the second postoperative day. When patients requested further analgesia, they received a single, identical capsule of either oral delta-9-THC 5 mg (n=20) or placebo (n=20) in a double-blind fashion. The primary outcome measure was summed pain intensity difference (SPID) at 6 h after administration of study medication derived from visual analogue pain scores on movement and at rest. Secondary outcome measures were time to rescue medication and adverse effects of study medication. Mean (SD) VAS pain scores before medication in the placebo and delta-9-THC groups were 6.3(2.6) and 6.4(1.3)cm on movement, and 3.2(1.9) and 3.3(0.9) on rest, respectively. There were no significant differences in mean (95% confidence interval of the difference) SPID at 6 h between the groups [placebo 7.9, delta-9-THC 4.3(-1.8 to 9.0)cm h on movement; placebo 8.8, delta-9-THC 4.9(-0.2 to 8.1)cm h at rest] and time to rescue analgesia [placebo 217, delta-9-THC 163(-22 to 130)min]. Increased awareness of surroundings was reported more frequently in patients receiving delta-9-THC (40 vs 5%, P=0.04). There were no other significant differences with respect to adverse events. This study demonstrates no evidence of an analgesic effect of orally administered delta-9-THC 5 mg in postoperative pain in humans.