Background and Purpose-Patients with chronic kidney disease (CKD) are at a particularly high risk for ischemic and bleeding events. Limited data exist as to the efficacy and safety of clopidogrel in stroke patients with renal dysfunction. Therefore, we sought to assess the impact of decreased kidney function on clinical outcomes for stroke patients on clopidogrel-aspirin treatment. Methods-Patients in the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) were randomized to clopidogrel-aspirin or aspirin-alone treatment. The primary efficacy outcome was new stroke during 90 days, whereas bleeding was the safety outcome. Patients were stratified according to estimated glomerular filtration rate. Results-Dual clopidogrel-aspirin therapy was associated with a marked reduction in new strokes compared with the therapy of aspirin alone in patients with normal renal function (hazard ratio, 0.77; 95% confidence interval, 0.60-0.98; P=0.02) and mild CKD (hazard ratio, 0.60; 95% confidence interval, 0.45-0.79; P<0.01), whereas in patients with moderate CKD, no significant benefit from clopidogrel therapy was detected (hazard ratio, 1.00; 95% confidence interval, 0.43-2.35; P=0.99). There was no clear difference in bleeding episodes by treatment assignment across categories of renal impairment. Conclusions-Clopidogrel plus aspirin could decrease new stroke in patients with normal kidney function and mild CKD, but no extra benefit was observed in those with moderate CKD. Bleeding risk from the dual therapy did not seem to increase in mild or moderate CKD patients.