Abstract Background Cardiovascular disease (CVD) is the most common complication and the leading cause of death in patients with chronic kidney disease (CKD). Accelerated atherosclerosis is a pathophysiological process that is vital to the occurrence of cardiovascular complications associated with CKD. Abnormal platelet activation is not only the leading cause of atherosclerosis but also plays a critical role in the occurrence of thrombotic events. Currently, antiplatelet drugs are commonly used as a secondary prevention strategy for high blood pressure, obesity, diabetes, and ischemic heart disease and can reduce the risk of CVD in the susceptible population. However, the benefits and evidence of using antiplatelet agents in patients with CKD remain controversial. This study aimed to determine whether antiplatelet therapy can safely prevent atherosclerosis in patients with CKD in the primary care setting. Methods/design The ALTAS-CKD study is a multicenter, prospective, randomized, double-blind, placebo-controlled trial of 554 adult patients with stage 3–5 non-dialysis-dependent CKD recruited from 10 territory medical centers in China. A secured web-based computer randomization system will be used to administer aspirin 100 mg once daily or a matching inactive placebo for 36 months. The primary endpoint will be the occurrence of atherosclerosis, as measured by carotid ultrasonography. The secondary endpoints will be combined cardiovascular events, all-cause mortality, and 50% decrease in the estimated glomerular filtration rate. Trial registration {2a} Current controlled trials number: ChiCTR1900021393. Registered on 18 February 2019.