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Background Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and oral P2Y12 inhibitor (P2Y12-I) represents the standard of care for patients with acute coronary syndromes (ACS) or with chronic coronary syndromes (CCS) treated with percutaneous coronary intervention (PCI). Cangrelor, the first intravenous P2Y12-I, is deemed to overcome the drawbacks of the oral administration; nevertheless real world data on this new drug are scanty. We sought to investigate routine clinical use of cangrelor in four interventional centers of Italy. Methods We enrolled 241 consecutive patients (196 ACS, 45 CCS) treated with cangrelor during PCI. Drug administration modalities and in-hospital clinical outcomes were evaluated. A subanalysis in patients selected on the basis of the CHAMPION Phoenix trial inclusion/exclusion criteria (CHAMPION-like subpopulation) was also performed. Results Cangrelor was mainly utilized in ACS patients, who presented poorer clinical conditions and higher bleeding risk. Cangrelor was given only in P2Y12-I naive patients; switch to clopidogrel was always done at the end of the infusion, while ticagrelor or prasugrel were prevalently given 30 minutes before. In-hospital mortality was 10.0% and GUSTO moderate/severe bleeding was 2.5%. Bleeding data showed nevertheless to be in line with the CHAMPION Phoenix results in the "CHAMPION-like" subpopulation. Conclusions Cangrelor was predominantly used in ACS with modalities substantially in accord with the label indications. Poor clinical outcomes are due to the prevalent utilization in highly challenging clinical settings, nevertheless the rate of bleeding and stent thrombosis are in line with the randomized trials if analyzed in a subpopulation of comparable risk profile.