Objective To evaluate the benefits of antiplatelet therapy in reducing all-cause mortality and cardiovascular disease (CVD) mortality in elderly chronic kidney disease (CKD) patients with high CVD risk. Methods Based on the data of the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018, the elderly CKD participants with high risk of CVD were analyzed. Results A total of 5 316 elderly CKD patients with high risk of CVD were included. Among them, 557 cases used antiplatelet agents and 4 759 did not use antiplatelet drugs. Compared with the non-antiplatelet therapy group, the risk of all-cause mortality in the antiplatelet therapy group was not significantly increased (adjusted hazard ratio [HR]＝1.13, 95% confidence interval [95%CI] 0.97-1.30; adjusted HR＝1.24, 95%CI 0.99-1.55). In elderly CKD patients without CVD (primary prevention), compared with the non-antiplatelet therapy group, the risks of all-cause mortality and CVD mortality in the antiplatelet therapy group were not significantly increased (adjusted HR＝1.04, 95%CI 0.79-1.37; adjusted HR＝1.13, 95%CI 0.71-1.78). In elderly CKD patients with CVD (secondary prevention), the risks of all-cause mortality and CVD mortality in the antiplatelet therapy group were not significantly higher than those in the non-antiplatelet therapy group (adjusted HR＝1.15, 95%CI 0.96-1.36; adjusted HR＝1.23, 95%CI 0.96-1.58). When stratified by estimated glomerular filtration rate (eGFR) (＜45, 45-＜60, ≥60 mL/[min·1.73 m²] or urinary albumin creatinine ratio (＜30, 30-＜300, ≥300 mg/g), there were no significant differences in all-cause mortality risk or CVD mortality risk between the 2 group (both P＞0.05). Conclusion Antiplatelet agents are not associated with the reduction in all-cause mortality or CVD mortality in elder CKD population with high CVD risk, and the results are consistent across primary and/or secondary prevention, different eGFR and proteinuria categories.