Background: Post dural puncture headache (PDPH) is a major challenging complication and may be a cause of morbidity after spinal anesthesia. Currently there is no definitive management for PDPH, so the search for effective treatment continues. Objectives: Our aim was to investigate the analgesic effectiveness of oral prednisolone vs oral pregabalin for managing PDPH subsequent to spinal anesthesia for lower limb surgeries. Study Design: A prospective controlled double-blind randomized study. Setting: Academic University Hospitals. Methods: A total of 63 patients who had lower limb surgeries and suffered PDPH after spinal anesthesia were randomly allocated into one of 3 groups. Group C patients received conservative treatment and to maintain blinding, a tablet of vitamins was given to them twice per day for 3 days; Group P patients received conservative treatment and oral prednisolone 20 mg once daily plus one tablet of vitamins (in order to ensure blinding) for 3 days; Group G patients received oral pregabalin 150 mg twice daily for 3 days in addition to conservative treatment. The primary outcomes we measured were the Visual Analog Scale (VAS) score and modified Lybecker score. The secondary outcomes we measured were the total dose of rescue analgesia, the need for an epidural blood patch (EBP), and adverse effects from the study drugs. Results: When comparing the intensity of headaches assessed through both the VAS and the modified Lybecker score, no statistically significant disparities were observed in relation to baseline measurements. While after starting treatment by 12 hours and 24 hours, the headache intensity was statistically significantly lower in Group G compared to Group P and Group C, but there was no significant difference between Group C and Group P at 12 hours. The headache intensity was statistically significantly higher in Group C compared to Group P and Group G, but there was no significant difference between Group P and Group G at 48 hours and 72 hours. Ketorolac consumption was statistically significantly higher in group C than the other groups. However, it was statistically significantly lower in group G than group P. Only 2 patients in group C were indicated for EBP while no patients in either Groups P or G required an EBP. Limitations: Our study’s limitations include the paucity of literature studying prednisolone and pregabalin use in PDPH, our study’s small sample size, and the lack of sufficient studies for comparing results may limit the generalization of our findings. Conclusion: Both oral prednisolone and pregabalin were effective in reducing PDPH severity; oral pregabalin is superior to prednisolone.