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Addition of an opioid to low-dose spinal anesthesia with bupivacaine improves the quality and success of anesthesia. However, the intrathecal fentanyl-induced pruritus is as high as 75%. We hypothesized that after administration of 4 or 8 mg of prophylactic IV ondansetron, the incidence of pruritus induced by low-dose intrathecal fentanyl would be significantly lower than after placebo.In this double-blind study, 90 outpatients undergoing knee arthroscopy received 3 mg of bupivacaine + 10 μg fentanyl intrathecally. Before spinal puncture, the patients received randomly either saline (P) or ondansetron 4 mg (O4) or 8 mg (O8) IV. They were asked about pruritus frequently, and they estimated its severity on a scale of 0–10.There was no difference in the incidence of pruritus between the three groups: pruritus occurred in 17 (57%), in 21 (75%) and in 19 patients (70%) in P, O4 and O8 groups, respectively. The pruritus was mostly mild. Four patients in the placebo group, three in the O4 and four patients in the O8 groups considered it severe. One patient in each group requested treatment for pruritus; after IV naloxone their pruritus was relieved. Neither time to pruritus nor duration of pruritus differed between the groups. One patient in each group developed a long-lasting (> 10 h) pruritus.After prophylactic administration of 4 or 8 mg of ondansetron IV, the incidence, duration and severity of pruritus were similar to placebo. Ondansetron does not prevent pruritus induced by low-dose intrathecal fentanyl.