Patients undergoing percutaneous coronary intervention (PCI) often have high-bleeding-risk (HBR) factors. Dual antiplatelet therapy (DAPT) further increases this risk of bleeding. We sought to compare clinical outcomes according to presence or absence of HBR factors in patients with elevated ischemic risk (DAPT score ≥ 2) undergoing PCI. We evaluated all patients undergoing PCI at MedStar Washington Hospital Center (January 2009 to July 2018) with DAPT score ≥2, which is associated with elevated risk of ischemic events. Patients were categorized as HBR group (HBR score ≥1) or low-bleeding-risk (LBR) group (HBR score = 0). Outcomes included major adverse cardiac events such as target vessel revascularization, stent thrombosis, death, and bleeding events at 30 days, 6 months, 1 year, and 2 years. The final cohort consisted of 7,499 patients: 3,949 patients had LBR features, and 3,550 patients had HBR features. The 2 groups were different at baseline, with HBR patients being older and having a higher prevalence of congestive heart failure and renal dysfunction than the LBR group. The mean DAPT score was 2.96±1.1 for the LBR group and 3.7±1.4 for the HBR group (p <0.001). During follow-up at 30 days, 6 months, and 1 and 2 years, the rates of target vessel revascularization and stent thrombosis were not significantly different between the 2 groups. Bleeding events and all-cause mortality were significantly more frequent in the HBR group than in the LBR group. In conclusion, patients undergoing PCI often have pre-existing risk factors that predispose them to ischemic and bleeding complications. Prolonged duration of DAPT to mitigate ischemic events could lead to a disproportionate increase in bleeding events, especially in HBR patients.