Essentials Anti-activated factor X (Anti-Xa) monitoring is more precise than activated partial thromboplastin (aPTT). 20 804 hospitalized cardiovascular patients monitored with Anti-Xa or aPTT were analyzed. Adjusted transfusion rates were significantly lower for patients monitored with Anti-Xa. Adoption of Anti-Xa protocols could reduce transfusions among cardiovascular patients in the US. SUMMARY:Background Anticoagulant activated factor X protein (Anti-Xa) has been shown to be a more precise monitoring tool than activated partial thromboplastin time (aPTT) for patients receiving unfractionated heparin (UFH) anticoagulation therapy. Objectives To compare red blood cell (RBC) transfusions between patients receiving UFH who are monitored with Anti-Xa and those monitored with aPTT. Patients/Methods A retrospective cohort study was conducted on patients diagnosed with acute coronary syndrome (ACS) (N = 14 822), diagnosed with ischemic stroke (STK) (N = 1568) or with a principal diagnosis of venous thromboembolism (VTE) (N = 4414) in the MedAssets data from January 2009 to December 2013. Anti-Xa and aPTT groups were identified from hospital billing details, with both brand and generic name as search criteria. Propensity score techniques were used to match Anti-Xa cases to aPTT controls. RBC transfusions were identified from hospital billing data. Multivariable logistic regression was used to identify significant drivers of transfusions. Results Anti-Xa patients had fewer RBC transfusions than aPTT patients in the ACS population (difference 17.5%; 95% confidence interval [CI] 16.4-18.7%), the STK population (difference 8.2%; 95% CI 4.4-11.9%), and the VTE population (difference 4.7%; 95% CI 3.3-6.1%). After controlling for patient age and gender, diagnostic risks (e.g. anemia, renal insufficiency, and trauma), and invasive procedures (e.g. cardiac catheterization, hemodialysis, and coronary artery bypass graft), Anti-Xa patients were less likely to have a transfusion while hospitalized for ACS (odds ratio [OR] 0.16, 95% CI 0.14-0.18), STK (OR 0.41, 95% CI 0.29-0.57), and VTE (OR 0.35, 95% CI 0.26-0.48). Conclusion Anti-Xa monitoring was associated with a significant reduction in RBC transfusions as compared with aPTT monitoring alone.