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Vascular surgery patients often require anticoagulation with intravenous unfractionated heparin monitored through antifactor Xa (anti-Xa) levels or the activated partial thromboplastin time (aPTT). This study compares the 2 monitoring strategies in terms of major bleeding events in the vascular surgery population.This was a single-center, retrospective study that included patients treated with a pharmacy-managed heparin protocol monitored by either anti-Xa or aPTT after vascular surgery. The primary outcome was the percentage of patients experiencing major bleeding events after procedure. Secondary outcomes evaluated minor bleeding episodes, postprocedure packed red blood cell transfusions, and the incidence of thrombotic events. In a secondary analysis, simultaneously measured anti-Xa and aPTT values were identified and analyzed for discordance.Major bleeding occurred in 12/72 patients (17%) on the anti-Xa–monitored protocol versus 5/62 patients (8%) on the aPTT-monitored protocol (P = 0.19). Minor bleeding episodes were documented in 10% of the patients in the anti-Xa group versus 6% in the aPTT group (P = 0.54). There were no significant differences between the 2 groups in packed red blood cell transfusions and thrombotic events. Of 109 pairs of simultaneously measured anti-Xa and aPTT values, 39 pairs (36%) showed relatively high aPTT values compared with corresponding anti-Xa levels. Nine patients who had these discordant test results experienced bleeding while their heparin drip was titrated based on lower anti-Xa values.The use of anti-Xa levels for heparin titration showed higher rates of major bleeding complications in vascular surgery patients compared with aPTT monitoring, but no significant difference was identified in this study. Vascular surgery patients with relatively high aPTT to anti-Xa values may have an increased risk of bleeding complications when heparin is titrated based on anti-Xa levels.