OBJECTIVES: The study aim was to compare cost and resource utilization between patients receiving unfractionated heparin (UFH) monitored with Antifactor Xa (Anti-Xa) and those monitored with activated partial thromboplastin (aPTT).  METHODS: A retrospective cohort study was conducted on patients diagnosed with acute coronary syndrome (ACS, N=14,822), ischemic stroke (STK, N=1,568) or (VTE, N=4,414) in the MedAssets data from January 2009 to December 2013. Anti-Xa and aPTT cohorts were identified from hospital billing detail records. Propensity score techniques were used to match Anti-Xa cases to aPTT controls. Overall inpatient cost was the primary measure of utilization. Multivariate regression models were used to determine differences in utilization between groups.  RESULTS: In the matched sample the average patient age was 66.7 (ACS), 68.0 (STK) and 63.1 (VTE) years.  Percent female was 37.2% (ACS), 49.4% (STK), and 52.2% (VTE). The average Charlson index was 3.8 (ACS), 4.7 (STK), and 2.7 (VTE). In post-match unadjusted comparisons the Anti-Xa cohort had significantly lower median cost in each subpopulation (ACS $17,161.96 vs. $21,143.68, p<.0001; STK $17,386.94 vs. $20,841.29, p<.0001; VTE $7,922.62 vs. $8,730.31, p = 0.0022). After controlling for patient age and gender, diagnostic risks (e.g. anemia, renal insufficiency, trauma) and invasive procedures (e.g. cardiac catheterization, hemodialysis, coronary artery bypass graft, red blood cell transfusions), Anti-Xa patients were predicted to have lower hospital costs (ACS RR=0.83, p=0.0048; STK RR=0.9034,  p=0.0007; VTE RR: 0.96, p=0.0442). Transfusions were the most impactful driver of cost (ACS RR=1.94, p=0.0062; STK RR=1.54, p<0.0001; VTE RR=1.56, p<0.0001). Post hoc analysis indicated Anti-Xa patients were less likely have a transfusion (ACS OR=0.16, CI=0.14-0.18; STK OR=0.41, CI=0.29-0.57; VTE OR=0.35, CI=0.26-0.48).  CONCLUSIONS: UFH patients monitored by Anti-Xa have lower hospitalization costs compared to aTTP patients. These differences may be driven by lower transfusion rates in the Anti-Xa sample.