Background: Lab tests such as activated partial thromboplastin time (aPTT) or anti–factor Xa (anti-Xa) levels are typically used to monitor intravenous unfractionated heparin (IV heparin), with recent evidence suggesting that anti-Xa levels may provide a more accurate measure of anticoagulation. Objective: The Lexington Veterans Affairs Health Care System transitioned from using aPTT to anti-Xa levels in January 2017. This study was conducted to evaluate the efficacy and safety of this change. Methods: This was a retrospective cohort study comparing all patients receiving IV heparin per protocol for at least 24 hours from August 1, 2016, to January 31, 2017 (aPTT group), and February 1, 2017, to July 31, 2017 (anti-Xa group). The primary objective was a comparison of IV heparin doses required to achieve goal range between the 2 cohorts. Secondary objectives included a comparison of time to therapeutic goal, percentage of time within goal range, number of rate changes until therapeutic goal, and adverse outcomes, such as number of bleeds. Results: A total of 155 patients were included in this study. Significantly higher IV heparin doses were required to achieve therapeutic goal in the anti-Xa group, despite significantly fewer IV heparin rate changes required. Anti-Xa monitoring was not associated with an increased risk of adverse events. Conclusion and Relevance: Significantly higher IV heparin doses were required to achieve therapeutic anti-Xa levels after transitioning from an aPTT-based protocol in the largely unstudied veteran population. However, the transition from aPTT to anti-Xa monitoring appears safe and efficacious in these patients.