Purpose To assess the efficacy of a novel preemptive multimodal analgesic regimen for reducing postoperative pain and complications after primary lumbar fusion surgery. Preemptive multimodal analgesia is revealed to be an effective alternative to conventional morphine administration providing improved postoperative pain control with diminished side effects. However, an optimal regimen for spinal fusion surgery remains unknown. Methods After Institutional Review Board approval, 80 patients who underwent primary lumbar 4-5 fusion surgery were randomly assigned to receive either only intravenous morphine or a preemptive multimodal (celecoxib, pregabalin, extended-release oxycodone, and acetaminophen) analgesic regimen. Postoperative pain and functional levels were measured by the visual analog scale (VAS) and Oswestry Disability Index (ODI), respectively, and intraoperative blood loss, postoperative Hemovac drain output, and nonunion rates were evaluated for complications. Results No differences were observed in the patient demographics, intraoperative blood loss, postoperative Hemovac drain output, or nonunion rate between two groups. The VAS and ODI were lower at all postoperative time points, except the ODI on postoperative day 1 in patients randomized to receive the preemptive multimodal analgesic regimen. No major identifiable postoperative complications were observed in either treatment group. Conclusions The preemptive multimodal analgesic combination in this study appears to be safe and effective after lumbar fusion surgery.