Background: Although pregabalin and gabapentin have been used to control pain after spinal surgery, there is little evidence comparing their analgesic advantages to opioids. Objective: The current study aimed to assess efficacy and safety of analgesia with pregabalin versus gabapentin compared to opioids in patients undergoing elective lumbar microdiscectomy. Methods: This randomized-controlled trial included 72 patients scheduled for elective lumbar microdiscectomy. The patients were randomly allocated to three groups. Each group enrolled 24 patients who received 0.1 mg/kg of morphine intramuscularly 30 minutes before the surgery. One hour before the surgery, 150 mg of pregabalin was given orally for the pregabalin (P) group, meanwhile, in the gabapentin (G) group, 400 mg of gabapentin were given orally, and in the control (C) group, 100 micrograms of vitamin B12 were given orally. The primary outcome was the time to first rescue analgesia. The secondary outcomes were the intraoperative hemodynamics, visual analogue score, total consumption of morphine during the first postoperative 24 h, and morphine complications. Results: Groups P and G had significantly longer time to first analgesia and significantly lower total morphine consumption during the first 24 h and visual analogue scores at 10, 12, 16, 20, and 24 hours postoperatively. All groups had comparable hemodynamic parameters and postoperative complications. Conclusion: In elective lumbar microdiscectomy, preoperative administration of pregabalin provided longer time to first rescue analgesia with better acute pain control and lower total analgesic consumption compared to gabapentin and opioid analgesia.