Background and Objective: Post-operative nausea and vomiting (PONV) is a common adverse effect of the anesthesia in laparoscopic surgery. Ondansetron has been used for prevention and treatment of the PONV. The purpose of the present study was to compare the effects of preemptive and preventive intravenous ondansetron on PONV in patients undergoing diagnostic gynecologic laparoscopy. Materials & Methods: In a randomized double-blind clinical trial, 80 women candidate of diagnostic laparoscopy, were enrolled to study in two preemptive or preventive groups (n = 40). Ondansetron 4 mg IV was administered 5 min before anesthesia induction or 5 min before extubation in preemptive or preventive groups, respectively. The frequency and severity of the PONV were compared at post-anesthetic care unit (PACU), 3th, 6th and 24th postoperatively in two groups. Also the first time of need for the antiemetic drug was studied. Results: Demographic data were similar but duration of anesthesia was shorter in preventive group. The PONV rate was similar in two groups [(37.5% and 32.5% in preemptive and preventive groups, respectively (P = 0.815)]. In preemptive group it was more intense at PACU and 24 hours after surgery (P-value <0.05) and rate of vomiting was high (11 vs. 3, P-value 0.037). The first request for antiemetic drug was earlier and the antiemetic consumption dose (P-value <0.05), recovery and hospital stay times were high in preemptive group (P-value = 0.001). Conclusion: Preventive ondansetron is more effective than preemptive form, in reducing the severity of PONV but not rate of the PONV in diagnostic gynecologic laparoscopy.