Background & Objective: Evidence about the effect of theophylline and gabapentin on post-spinal headache is rare.Therefore, in this study, we compared the effect of gabapentin and theophylline on post-spinal headache after cesarean section. Materials & Methods:We conducted a double-blind randomized clinical trial on 120 pregnant women, who underwent spinal anesthesia due to cesarean section; they had experienced post-spinal headache.They were randomly assigned to the study groups, including gabapentin and theophylline groups.The gabapentin group received 400 mg of gabapentin, every eight hours for 24 hours.The theophylline group also received 200 mg theophylline, every eight hours for 24 hours.The visual analog scale (VAS) score was compared between the two groups before the intervention and 8, 16 and 24 hours after the intervention.Statistical analysis was done using Student's t-test.P-value less than 5% was considered as significant.Results: There was not any significant difference between the two groups in regards of VAS score, before the intervention and 8 and 16 hours after the intervention; the significant lower VAS score was reported by the theophylline group, 24 hours after the intervention (0.7±1.79 vs. 2.23±2.58,P=0.014).Reductions in the VAS score during 8 hours (3.14 vs. 2.67), 16 hours (4.7 vs. 3.47) and 24 hours (5.5 vs. 3.8) were compared after the intervention; it was higher in the post-intervention compared to the pre-intervention in the theophylline group. Conclusion:The present clinical trial study showed that reduction in the VAS score was significantly higher in the theophylline group compared to the gabapentin group, only within 24 hours.Both gabapentin and theophylline were effective against post-spinal headache, but Theophylline was more effective on pain relief within 24 hours.