OBJECTIVES: Intracoronary atherothrombosis complicates percutaneous coronary intervention (PCI). Cangrelor, a novel, intravenous P2Y12 inhibitor reduced the risk of death, MI, ischemia-driven revascularization and stent thrombosis at 48 hours by 22% compared to clopidogrel in the CHAMPION PHOENIX Trial. An economic sub-study was designed, from the perspective of the US healthcare system, to determine the direct medical costs during index hospitalization among cangrelor vs. clopidogrel patients and the subgroup receiving bivalirudin as antithrombin therapy. METHODS: Hospital bills were collected from participating US sites in the CHAMPION PHOENIX trial. Hospital costs were determined by multiplying itemized hospital charges and the cost-center specific cost-to-charge ratios obtained from hospital's Medicare Cost Report (MCR).  A model predicting in-hospital costs was developed by utilizing multivariate imputation by chained equations (MICE) methodology. The costs were imputed for patients where clinical but not economic data were available. After imputation, the index hospital costs from entire US population were compared between treatment groups. RESULTS: Thirty-eight US sites were invited and 22 participated. One site was excluded due to incomplete MCR. Hospital bills from 1117 patients (27.3% of 4,097 CHAMPION PHOENIX US population) were utilized. Patients’ baseline characteristics and complications were similar to the rest of US population. After the MICE imputation, the index hospitalization costs of patients receiving cangrelor and clopidogrel were not statistically different ($11,755 cangrelor vs. $11,914 clopidogrel, P=NS, difference=$159) even when bivalirudin as the anticoagulant was utilized ($12,941 cangrelor/bivalirudin vs. $13,216 clopidogrel/bivalirudin, P=NS, difference=$275). Data also shows a numerical saving of $109 for catheterization laboratory costs among cangrelor-treated patients ($9,030 vs. $9,139, P=NS) with similar results among bivalirudin subgroup. CONCLUSIONS: This analysis reveals similar direct medical costs, from the perspective of the US healthcare system, for cangrelor patients (with or without bivalirudin) during the index hospitalization and catheterization laboratory in the CHAMPION PHOENIX trial.