Background: Although the most popular anesthesia technique for cesarean is spinal anesthesia, its most common complication is post-dural puncture headache (PDPH). Aim: We aimed to determine the effect of median and paramedian approaches during spinal anesthesia on PDPH in patients undergoing cesarean section. Subjects and Methods: 200 pregnant women between the ages of 19-45 years, ASA physical status II, scheduled to undergo elective cesarean section under spinal anesthesia, were studied. The patients were randomized into two groups: Group M; (n = 100) spinal anesthesia with the median approach, Group PM; (n = 100) spinal anesthesia with paramedian approach. The patients were questioned for the possible occurrence of PDPH on the first, third and seventh postoperative days. A telephone follow-up call was used if the hospital stay was shorter than seven days. Post-dural puncture headache was evaluated according to the International Classification of Headache Disorders (ICHD-III) diagnostic criteria. Normally distributed data were summarized using mean and standard deviation. Skewed data were summarized using median (range). Results: A total of 200 patients completed the study. There were no statistically different between the groups by comparing the incidence and characteristics of PDPH (32% vs. 28%, P = 0.548). Most patients rated their pain intensity during PDPH as mild to moderate in both groups (p = 0.721). PDPH onset time was 2 (1-4) days in Group PM versus 3 (1-7) days in Group M (p = 0.173). No patient needed for epidural blood patch in both groups. Conclusions: Spinal anesthesia with a median or paramedian approach at cesarean section has no effect on the incidence of PDPH, but we believe that there has been a need for further studies with larger or different patient populations.