BACKGROUND: Propofol injection pain is a common problem that can be very distressing for patients. We compared the effects of injection with saline followed by injection with a fentanyl-propofol mixture, injection with fentanyl followed by a propofol injection, and injection with saline followed by propofol alone on propofol injection pain. METHODS: The patients were assigned randomly to one of three groups. A rubber tourniquet was placed on the forearm to produce venous occlusion for 1 min. Before anesthesia induction, group C (control, n = 50) and group M (fentanylpropofol mixture, n = 50) received 5 ml of isotonic saline, while group F (fentanyl, n = 50) received 2 microg/kg of fentanyl. After the tourniquet was released, groups C and F received 5 ml of propofol and group M received 5 ml of a mixture containing 20 ml of propofol and 4 ml of fentanyl. At 10 s after the study drugs were given, a standard question about the comfort of the injection was asked of the patient. We used a verbal rating scale to evaluate propofol injection pain. Statistical analyses were performed with Student's t-tests and Fisher's exact tests; P < 0.05 was considered to indicate statistical significance. RESULTS: The demographic data were similar among the groups. In group M, the number of patients reporting propofol injection pain was significantly lower than in groups F and C (both P < 0.001). No patient in group F or M experienced severe pain, whereas 24 patients (48%) had severe pain in group C (both P < 0.001). CONCLUSIONS: This study shows that a fentanyl-propofol mixture was more effective than fentanyl pretreatment or a placebo in preventing propofol injection pain.