Objective To investigate the efficacy and safety of ondansetron during cesarean section under spinal anesthesia. Methods We sought randomized controlled trials (RCTs) on ondansetron during spinal anesthesia for cesarean section in The Cochrane Library, PubMed, MEDLINE, and Web of Science from their inception to September 2016. Results Altogether, 21 RCTs were included in this study. Meta-analysis showed that the ondansetron group had a lower incidence of nausea/vomiting and bradycardia than the placebo group during cesarean section under spinal anesthesia [relative risk (RR)=0.43, 95% confidence interval (CI) (0.36, 0.51) and RR=0.45, 95% CI (0.26, 0.80), respectively]. There were no significant differences in the incidences of pruritus, hypotension, or shivering during cesarean section under spinal anesthesia [RR=0.92, 95% CI (0.83, 1.02); RR=0.72 (0.50, 1.06), 95% CI (0.50, 1.06); and RR=0.89, 95% CI (0.71, 1.11), respectively]. Conclusion Ondansetron effectively reduces the incidences of nausea/vomiting and bradycardia under spinal anesthesia during cesarean section.