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The innovative pharmacological combination of low-dose rivaroxaban plus aspirin provides clinicians with an ideal opportunity to intensify the medical treatment of patients with coronary artery disease (CAD) and comorbid peripheral artery disease (PAD). We aimed to determine the cost-effectiveness of PAD screening using the ankle-brachial index (ABI) test in patients with CAD (with rivaroxaban administered if the PAD screening was positive) compared with no-screening strategy in China. A Markov decision model using a 1-month cycle was developed to simulate the 25-year effectiveness and cost of PAD screening on 75-year-old patients with CAD in China, evaluating the quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way, two-way, and probabilistic sensitivity analyses were conducted to assess the impact of variations in the key parameters for ICERs. Our model found an incremental cost of RMB4,959 (US$740) and an incremental QALY of 0.054 after one-time ABI screening, leading to an ICER of RMB91,936 (US$13,717) per QALY gained over a 25-year period. The reduction in all-cause mortality related to rivaroxaban and its cost were the factors most affecting the ICER. The screening would become cost-effective by decreasing the monthly cost of rivaroxaban to RMB184.5 (US$27.5) or by using domestic-brand rivaroxaban according to the threshold of a willingness to pay RMB72,447 (US$10,809) per QALY gained. Our study demonstrated that ABI screening for PAD to decide on low-dose rivaroxaban administration was not cost-effective for patients with CAD in China. Nevertheless, policy-guided cost changes for domestic-brand rivaroxaban could easily resolve this issue. • ABI screening for PAD was not cost-effective for patients with CAD in China. • The reduction in all-cause mortality related to rivaroxaban most affected the ICER. • Policy-guided cost changes for rivaroxaban could easily resolve this issue in China. [ABSTRACT FROM AUTHOR]