Background China is facing a more severe stroke challenge. In 2017, China fully implemented the zero-margin drug policy (ZMDP), cancelling 15% of drug markups in public hospitals. Based on the “System of Health Accounts 2011” (SHA 2011), this paper explores the changes in the economic burden of stroke in China after implementing ZMDP to provide an accurate reference for policymakers. Methods Stroke patients from 2016 to 2018 were selected by multistage stratification probability-proportional random sampling in Shanxi Province. A total of 223 187 samples were included. Regression discontinuity design (RDD) was used to measure the change of drug proportion and cost. Sensitivity analysis and subgroup analysis were implied to determine the stability of the results. Results The current curative expenditure on stroke from 2016 to 2018 was 4374.69, 3727.22, and 3752.52 million Chinese Yuan (CNY). About 90% of the cost occurred during hospitalization, and 60% in general hospitals. After the implementation of ZMDP, the drug proportion from 46.54% (interquartile range (IQR) = 37.10%, 55.14%) in 2016 to 36.40% (IQR = 25.82%, 48.58%) in 2018, and average hospitalization cost per stay was from 7950.02 (IQR = 4938.76, 12 639.90) CNY in 2016 to 7362.08 (IQR = 4892.82, 11 501.40) CNY in 2018. RDD showed the drug proportion decreased by 2.76% (95% confidence interval (CI) = 1.17%, 4.35%, P = 0.001), and the expense decreased by 4698.34 (95% CI = 3047.59, 6349.09, P < 0.001) CNY. Conclusions The economic burden of stroke patients in China was severe. ZMDP played a noticeable effect in reducing drug proportion and hospitalization costs. The Chinese government should continue to implement relevant policies to control stroke costs according to regional and population characteristics.