We performed a systematic review to determine the overall efficacy of serotonin (5-HT3) receptor antagonists for the prevention and treatment of pruritus, nausea, and vomiting in women receiving spinal anesthesia with intrathecal morphine for cesarean delivery. Reports of randomized, controlled trials that compared prophylaxis or treatment of pruritus and/or nausea, and vomiting using one of the 5-HT3 receptor antagonists or placebo in women undergoing cesarean delivery were reviewed. The articles were scored for validity and data were extracted by the authors independently and summarized using relative risks (RR) with 95% confidence intervals (CI). Nine randomized, controlled trials were included in the systematic review. The nine trials had a total of 1152 patients enrolled; 539 received 5-HT3 receptor antagonists, 413 received placebo, and 200 received other antiemetics and were not included in the analysis. The incidence of pruritus was not reduced with 5-HT3 receptor antagonists prophylaxis compared with placebo (80.7% vs 85.8%, RR 95% CI = 0.94 0.81-1.09). However, their use reduced the incidence of severe pruritus and the need for treatment of pruritus (number-needed-to-treat = 12 and 15, respectively). Their use for the treatment of established pruritus showed improved efficacy compared with placebo with a number-needed-to-treat of three. There was a significant reduction in the incidence of postoperative nausea (22.0% vs 33.6%, RR 95% CI = 0.750.58-0.96) and vomiting (7.7% vs 16.8%, RR 95% CI = 0.49 0.30-0.81), and the need for postoperative rescue antiemetic treatment with the use of 5-HT(3) receptor antagonists when compared with placebo (9% vs 23%, RR 95% CI = 0.38 0.21-0.68). Although prophylactic 5-HT(3) receptor antagonists were ineffective in reducing the incidence of pruritus, they significantly reduced the severity and the need for treatment of pruritus, the incidence of postoperative nausea and vomiting, and the need for rescue antiemetic therapy in parturients who received intrathecal morphine for cesarean delivery. They were also effective for the treatment of established pruritus. Although more studies are warranted, the current data suggest that the routine prophylactic use of those drugs should be considered in this patient population.