Objective: The study aimed to evaluate the effectiveness of pain reduction between acetaminophen and gabapentin among postpartum patients, who undergo vaginal delivery. Materials and Methods: The present research was a randomized-controlled trial, enrolling term pregnant women with informed consent, who came to Phramongkutklao Hospital for vaginal delivery, between October 10, 2019 and March 15, 2020. Women with acetaminophen or gabapentin allergy, previously diagnosed with mood disorder or epilepsy, undergoing operative vaginal delivery, receiving epidural block or pudendal nerve block, not being able to understand Thai or English, need for general anesthesia, and taking other sedative agents within two hours before delivery were excluded. The participants were randomized into two groups by blocks of four and took medications, which were oral acetaminophen (500 mg) or gabapentin (300 mg). The medication was given at 30 minutes and six hours after delivery and the visual analog scale (VAS) was assessed at 30 minutes, 2- , 6- , and 12-hours. Side effects of each medication were also obtained. After 24 hours, postpartum depression was evaluated, using the Edinburgh postnatal depression scale. Data were statistically analyzed using SPSS and manifest mean ± standard deviation (SD). Results: Two hundred twenty patients randomly received either gabapentin (n=110) or acetaminophen (n=110). The VAS reduction of both groups and postpartum depression rate did not differ significantly (p=0.428). Women, taking gabapentin complained more about dizziness. Moreover, those taking acetaminophen experienced more drowsiness (p=0.757). Conclusion: Gabapentin and acetaminophen are not different, considering the effectiveness of pain control. In addition, side effects and efficacy of postpartum depression decrease were mostly similar.