BACKGROUND CONTEXT Posterior cervical decompression and fusion (PCDF) involves substantial blood loss, resulting in blood transfusions and associated complications, such as infections, hypotension and organ damage. The antifibrinolytic tranexamic acid (TXA), an inhibitor of the activation of plasminogen, has been shown to be beneficial in multiple surgical procedures without any apparent increase in postoperative complications. However, only a few studies report on TXA utilization in cervical spine surgery and there is currently no literature detailing the short-term safety of its use in this setting. PURPOSE To evaluate the short-term safety and efficacy of tranexamic acid use in multilevel posterior cervical decompression and fusion surgery. STUDY DESIGN/SETTING Retrospective case-control study from a single academic institution. PATIENT SAMPLE Forty-seven patients were identified to have undergone PCDF at our institution by one surgeon, 19 with the utilization of a TXA protocol and 28 patients without. Inclusion criteria were adults (age ≥18 years) with cervical stenosis and/or spondylosis who underwent cervical posterior spinal fusion surgery of at least 2 levels. OUTCOME MEASURES Intraoperative and postoperative blood loss and incidence of adverse events, including myocardial infarction (MI), acute renal failure, stroke, seizure, deep vein thrombosis (DVT) and pulmonary embolism (PE) were evaluated in the perioperative period and at 1-month follow-up. METHODS From January 2015 to April 2018, 47 patients were identified to have undergone PCDF, 19 with the utilization of a TXA protocol at our institution. Inclusion criteria were adults (age ≥18 years) with cervical stenosis and/or spondylosis who underwent cervical posterior spinal fusion surgery of at least 2 levels. The incidence of adverse events, including myocardial infarction (MI), acute renal failure, stroke, seizure, deep vein thrombosis (DVT) and pulmonary embolism (PE) were evaluated in the perioperative period and at 1-month follow-up. RESULTS Based on the inclusion criteria, 39 patients were selected. Nineteen (49%) received TXA as per our instructional protocol and 20 (51%) did not. Postoperative blood was significantly reduced (453ml vs 701ml; p = 0.03) in the group that received TXA. There was also a significant reduction in duration of surgery associated with TXA use (269 min vs 328 min; p = 0.05). There were no cardiac or thromboembolic complications on the first 30 days after surgical intervention on the TXA group, but there was a transient atrial fibrillation on the standard group. There were no infections, seizure activity, epidural hematomas or renal complications reported in either group. CONCLUSIONS TXA use during PCDF is a safe, effective method to reduce postoperative blood loss. Considering the limited number of patients in this study, these results should be validated on a larger group of patients. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.