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Study Design Retrospective matched analysis. Purpose To evaluate the effect of antithrombotic drug therapy on the rates of thrombo-ischemic or bleeding events 90 days following elective spine surgery. Overview of Literature Thrombo-ischemic and bleeding complications in patients undergoing spine surgery are major causes of morbidity. Many patients who pursue elective spine surgery are concurrently receiving antithrombotic therapy for unrelated conditions; however, at this time, the effects of preoperative antithrombotic use on postoperative bleeding and thrombosis are unclear. Methods Using an all-payer claims database, patients who underwent elective cervical and lumbar spine interventions between January 1, 2010, and June 30, 2018, were identified. Individuals were categorized into groups taking and not taking antithrombotics. A 1:1 analysis was constructed based on comorbidities found to be independently associated with bleeding or ischemic complications using logistic regression models. The primary outcomes were the rates of thrombo-ischemic events and bleeding complications. Results A total of 660,866 patients were eligible for inclusion. Following the matching procedure, 56,476 patient records were analyzed, with 28,238 in each group. The antithrombotic agent group had significantly greater odds of developing any 90-day thrombo-ischemic event after surgery: deep vein thrombosis (odds ratio [OR], 3.61; 95% confidence interval [CI], 3.06–4.25), pulmonary embolism (OR, 3.93; 95% CI, 3.34–4.62), myocardial infarction (OR, 6.20; 95% CI, 5.69–6.76), and ischemic stroke (OR, 3.76; 95% CI, 3.31–4.27). In addition, the antithrombotic agent group had an increased likelihood of experiencing hematoma (OR, 1.54; 95% CI, 1.35–1.76) and need for transfusion (OR, 2.61; 95% CI, 2.29–2.96). Conclusions Patients taking antithrombotic medications before elective surgery of the cervical and lumbar spine had increased risks of both ischemic and bleeding events. Spine surgeons should carefully consider these implications when appraising patients for surgery, given the lack of guidelines on perioperative management of antithrombotic agents.