BACKGROUND: High bleeding risk (HBR) and complex percutaneous coronary intervention (PCI) are major determinants for dual antiplatelet therapy (DAPT) duration. OBJECTIVES: The aim of this study was to evaluate the effects of HBR and complex PCI on short vs standard DAPT. METHODS: Subgroup analyses were conducted on the basis of Academic Research Consortium-defined HBR and complex PCI in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Verulam's-Eluting Cobalt-Chromium Stent-2) Total Cohort, which randomly compared clopidogrel monotherapy after 1-month DAPT with 12-month DAPT with aspirin and clopidogrel after PCI. The primary endpoint was the composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (Thrombolysis In Myocardial Infarction [TIMI] major or minor) endpoints at 1 year. RESULTS: Regardless of HBR (n=1, 893 [31.6%]) and complex PCI (n=999 [16.7%]), the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (HBR, 5.01% vs 5.14%; non-HBR, 1.90% vs 2.02%; P interaction=0.95) (complex PCI, 3.15% vs 4.07%; noncomplex PCI, 2.78% vs 2.82%; P interaction=0.48) and for the cardiovascular endpoint (HBR, 4.35% vs 3.52%; and non-HBR, 1.56% vs 1.22%; P interaction=0.90) (complex PCI, 2.53% vs 2.52%; noncomplex PCI, 2.38% vs 1.86%; P interaction=0.53), while it was lower for the bleeding endpoint (HBR, 0.66% vs 2.27%; non-HBR, 0.43% vs 0.85%; P interaction=0.36) (complex PCI, 0.63% vs 1.75%; noncomplex PCI, 0.48% vs 1.22%; P interaction=0.90). The absolute difference in the bleeding between 1- and 12-month DAPT was numerically greater in patients with HBR than in those without HBR (-1.61% vs-0.42%). CONCLUSIONS: The effects of 1-month DAPT relative to 12-month DAPT were consistent regardless of HBR and complex PCI. The absolute benefit of 1-month DAPT over 12-month DAPT in reducing major bleeding was numerically greater in patients with HBR than in those without HBR. Complex PCI might not be an appropriate determinant for DAPT durations after PCI. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent-2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498).