Unknown was the best antiplatelet therapy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) and chronic kidney disease (CKD). In the ISAR-REACT 5 trial, 2,364 patients with NSTE-ACS undergoing primarily percutaneous coronary intervention (PCI) were randomized to receive either ticagrelor or prasugrel. The estimated glomerular filtration rate (eGFR) was computed using the Chronic Kidney Disease Epidemiology Collaboration equation. The primary outcome measure was 1-year mortality. There were 85 deaths (3.6%): 6 deaths (17.1%) in patients with eGFR of less than 30, 31 deaths (6.9%) in patients with eGFR 30 to less than 60, 34 deaths (3.0%) in patients with eGFR 60 to less than 90, and 14 deaths (2.0%) in patients with eGFR of more than or equal to 90 ml/min/1.73 m2; adjusted hazard ratio (HR)=1.15, 95% CI 1.01 to 1.31; P=0.033 for 10 ml/min/1.73 m2 decrement in the eGFR. There was bleeding in 129 patients (5.5%): 7 bleeds (20.2%) in patients with eGFR of less than 30, 36 bleeds (8.0%) in patients with eGFR 30 to less than 60, 64 bleeds (5.6%) in patients with eGFR 60 to less than 90, and 22 bleeds (3.1%) in patients with eGFR more than or equal to 90 ml/min/1.73 m2; adjusted HR=1.11 (1.01 to 1.23); P=0.045 for 10 ml/min/1.73 m2 decrement in the eGFR. In conclusion, in patients with NSTE-ACS who underwent PCI with drug-eluting stents and third-generation antiplatelet medications, poor renal function was independently related to increased mortality risk and bleeding at 1 year. The ischemia and bleeding risks appeared to be comparable between ticagrelor and prasugrel across all categories of renal impairment.