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Background: There are many techniques to eliminate eye refractive errors. Photorefractive keratectomy (PRK) is one of these techniques causes an intensive post-surgical pain due to stimulation of pain receptors in the corneal epithelium. In this study we decided to compare the effect of two systemic drugs (Acifen and gabapentin) on pain relief following this surgery. Methods: In this double blind clinical trial study, 100 patients with refractive errors were divided into two groups with 50 members. A group of patients received gabapentin tablets (300 mg) every 8 hours for three days and the other group received Acifen capsules containing 325 mg acetaminophen, 200 mg ibuprofen, and 40 mg caffeine every 8 hours for three days. Patient's pain was measured through Faces Pain Scale (FPS). According to the findings, pain variables, drowsiness level, severity of dizziness, patient satisfaction and drug side-effects (before administration of drug, 2 hours after receiving each dosage) were determined and also compared between the two groups. Findings: There was no significant difference between the two groups in terms of age and sex. Pain assessment score median (P = 0.062), frequency of dizziness severity (P = 0.815), relative frequency of nausea and vomiting scores (P = 0.085), relative frequency of patient's satisfaction rate (P = 0.293), and frequency of drug side-effects (frequency in both groups equal to zero and P = 1) in the patients of the two groups had no significant difference to each other. Conclusion: The results of the present study showed no significant difference in comparing the two methods and considering other variables such as side effects, ease of use and also satisfaction rate, both methods can be used as successful methods to control pain in Photorefractive Keratectomy surgery. However, comparing either of the drugs with other methods of controlling pain seems necessary. [ABSTRACT FROM AUTHOR]