The study aimed to evaluate antiplatelet drug responsiveness in stable outpatients with cardiovascular disease and chronic kidney disease (CKD) and examine whether impaired antiplatelet drug responsiveness is associated with worse clinical outcomes in this population. Stable cardiovascular patients (n = 771) were enrolled at least one month after an acute ischemic atherothrombotic event. Antiplatelet drug responsiveness was assessed with specific assays (serum TxA2 for aspirin, the VASP assay for clopidogrel) and other aggregation-based assays using different agonists. All patients were followed until the first occurrence of a major adverse cardiovascular event. The 133 CKD patients were found to have higher activity of von Willebrand factor and higher fibrinogen levels. After a median follow-up of 33 months, 88 events occurred in patients without CKD and 31 events in patients with CKD (5.0 events and 8.7 events per 100 patient years, respectively, HR = 1.75 (95% CI 1.16-2.63; p = 0.008). The prevalence of poor aspirin and clopidogrel responsiveness and high platelet reactivity as assessed with different aggregation-based assays was similar in patients with estimated GFR ≥ 60 ml/min, 45-59 ml/min, and < 45 ml/min. No significant interaction for CKD vs. non-CKD was observed for events occurrence in patients with or without high platelet reactivity on several assays, with the exception of collagen-induced aggregation. In stable cardiovascular patients, CKD is not associated with higher platelet reactivity. Decreased antiplatelet drug responsiveness is not associated with worse clinical outcomes in CKD patients.