Background & Objectives: After cesarean delivery under spinal anesthesia with morphine, postoperative nausea and vomiting (PONV) may disturb maternal activity during breastfeeding and consequently reduce the successful rate of lactation. Prophylactic ondansetron may reduce the symptoms during breastfeeding within 24 hours post-delivery. Materials & Methods: In a randomized, double-blinded study, 158 healthy patients having cesarean delivery under spinal anesthesia with 0.2 mg of morphine were randomized to have either 4 mg of ondansetron (ondansetron group) or normal saline (control group) intravenously, immediately after delivery. The primary outcome was the incidence of nausea during the first rooming-in breastfeeding. Monitoring results within the following 24 hours, severity scoring by a four-point Likert Scale, and incidences of vomiting and itching were also compared. Results: Comparing the incidence of nausea between ondansetron and control groups, similarities were found during the first breastfeeding (24.2% vs 37.5%) and 24 hours post-delivery (3.8% vs 10.0%) (P=0.07 and 0.13). The ondansetron group returned fewer patients requiring rescued antiemetic in the post-anesthesia care unit (PACU) (5.1% vs 16.3%, P=0.02), but other incidences and severity of nausea were observed as similar to the control group. By regression analysis, the factors which reduced incidences of nausea in the PACU were ondansetron administration (P= 0.04, OR 0.28, 95%CI 0.08-0.96), and history of previous cesarean delivery (P= 0.04, OR 0.29, 95%CI 0.09-0.98). By contrast, post-delivery methylergometrine administration increased the rate of nausea (P= 0.04, OR 3.24, 95%CI 1.01-10.40). At 24 hours post-delivery, the association could be drawn only with history of PONV (P= 0.04, OR 2.72, 95%CI 1.04-7.12). Conclusion: The incidence of nausea was reduced by prophylactic ondansetron in the PACU, but not significantly different during breastfeeding on the same day and 24 hours post-operation. Therapeutic antiemetic may be appropriate and economical practice.