The opioid analgesic tramadol is a racemate and consists of 50% (+)- and 50% (-)-enantiomer. This study investigated analgesic efficacy and safety of both enantiomers after intravenous (i.v.) injection in comparison with the racemate. Ninety-eight patients recovering from major gynaecological surgery under opioid-free halothane anaesthesia were treated in a randomised, double-blind study with (+)-tramadol, (-)-tramadol or the racemate. Following an individualised i.v. loading dose up to a maximum of 200 mg, patient-controlled analgesia with demand doses of 20 mg was made available for 24 h. The primary criterion was of efficacy was the decrease of pain intensity on a 5-point verbal rating scale from severe or maximum pain to mild or no pain intensity on a 5-point verbal rating scale from severe or maximum pain to mild or no pain within the first hour after the loading dose. The secondary criterion was patient satisfaction with pain relief during the 24-h observation period stated in the final interview. Patients who terminated the study prematurely were evaluated as non-responders. Of patients treated with (+)-tramadol, tramadol racemate, and (-)-tramadol, 12%, 15%, and 53% of treated patients, respectively, terminated the study prematurely because of inefficacy. Of patients treated with (+)-tramadol, racemate or (-)-tramadol 67%, 48% and 38%, respectively, were considered responders regarding the primary criterion of efficacy (P = 0.061), and 82%, 76%, or 41% with respect to the secondary criterion (P = 0.001). Assessment of laboratory screening, adverse events, vital signs and blood gas monitoring showed no serious drug-related events. Nausea and vomiting were the most frequently reported non-serious side effects and were most often seen with (+)-tramadol. Taking into account both efficacy and safety aspects, the racemate seems to be superior to either enantiomer alone.