Background: Post-Dural puncture headache (PDPH) is a debilitating condition that appears after puncturing the dura mater. The headache is severe, throbbing, frontal, radiates to the occiput; increases by standing and decreases by lying down.

Objectives: This study aimed to compare the effect of ondansetron compared to neostigmine on reducing the incidence of PDPH in parturients undergoing spinal anesthesia for elective cesarean section.

Methods: we recruited 51 parturients undergoing spinal anesthesia for elective cesarean section were allocated into three equal groups at random; Group C: received intravenous injection of 0.9% normal saline after delivery of the fetus as controls, Group N: who received intravenous injection of neostigmine and atropine after delivery of the fetus, Group O: who received intravenous injection of ondansetron after delivery of the fetus.

Results: The patient's heart rate increased during spinal anesthesia, but it reduced throughout delivery and after drug infusion. The occurrence of headache and median visual analogue scale score at 48 and 7 days postpartum differed significantly among the three groups. The incidence of headache, median of VAS was higher among controls as compared to the neostigmine and the ondansetron group. Also, were higher in the neostigmine group compared to the ondansetron group. The control group (47.1%) required significantly more post-operative analgesia than the ondansetron group (11.8%; p=0.01). Conclusion: Intravenous injection of (0.08mg/kg) ondansetron is better to intravenous injection of (20g/kg) neostigmine + (10g/kg) atropine in lowering the incidence and severity of post-dural puncture headache in parturients undergoing spinal anesthesia for elective cesarean section.