Background: Currently, there are no validated tools to stratify bleeding risk in cancer patients undergoing percutaneous coronary intervention (PCI). The presence of cancer itself is considered a major high bleeding risk (HBR) feature according to the Academic Research Consortium (ARC) definition. However, cancer creates a hypercoagulable state and predisposes patients to thrombotic complications as well as bleeding. Hypothesis: A dedicated HBR definition for cancer patients undergoing PCI could be useful to identify subjects at higher risk of adverse events. Aims: To validate an adapted version of the ARC-HBR criteria in patients with cancer undergoing PCI. Methods: Consecutive patients with a history of cancer undergoing PCI between 2012 and 2022 at a tertiary care center (Mount Sinai Hospital, New York, US) were included. According to our adapted definition, patients were considered at HBR if they met at least one of the major ARC-HBR criteria (other than cancer) or two minor criteria. The primary endpoint was a composite of periprocedural in-hospital or post-discharge bleeding at 1 year. The key secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE) consisting of death, myocardial infarction, or stroke. Results: Of the 2,007 cancer patients included in this study, 1,142 (56.9%) were classified as HBR. Moderate to severe anemia was the most prevalent major HBR criterion ( Figure 1 ). At 1 year, the incidence of bleeding was significantly higher in HBR compared to non-HBR patients (10.9% vs. 3.9%, adj. HR: 2.10, 95% CI: 1.39-3.18, p<0.001), mainly driven by a higher risk of periprocedural bleeding (7.4% vs. 2.4%, p<0.001). Similarly, HBR patients were at higher risk of MACCE (11.0% vs. 3.2%, adj. HR: 2.33, 95% CI: 1.44-3.78, p<0.001) and death (8.8% vs. 2.2%, adj. HR: 2.59, 95% CI: 1.45-4.61, p=0.001) than non-HBR ones. Conclusions: An adapted version of the ARC-HBR definition, in which cancer is not a major criterion, effectively delineates cancer patients undergoing PCI who are at HBR. Cancer patients at HBR, according to this definition, also exhibit a higher risk of thrombotic events and mortality.