BackgroundChina proposed the Zero Markup Drug Policy (ZMDP), which popularized in tertiary hospitals across the country in 2017, to control drug expenditures’ rapid growth further and reduce the public’s medical burden. This study aims to evaluate the impact of ZMDP on the drug cost of chronic disease outpatients in the tertiary hospital in Chongqing.MethodsWe collected and described the drug-cost data for outpatients with chronic diseases in a Chongqing’s tertiary hospital from 2015 to 2019. The instantaneous and long-term changes of the outpatient volume and average drug cost after the ZMDP were evaluated using interrupted time series (ITS). We also analyzed the policy’s impact under the stratification of gender, age, and basic medical insurance types.ResultsA total of 350,848 outpatients were collected from January 2015 to February 2019. After the ZMDP, the outpatient volume for diabetes, hypertension, and coronary heart disease (CHD) all showed a downward trend, with a decrease of 53.04 (P = 0.012), 142.19 (P < 0.01) and 12.16 (P < 0.001) per month. Simultaneously, the average drug cost decreased by 4.44 yuan (P = 0.029), 5.87 yuan (P < 0.001) and 10.23 yuan (P = 0.036) per month, respectively. By gender, the average drug cost of diabetes in males had the most considerable instantaneous change, reducing by 51.21 yuan (P = 0.017); the decline of CHD in women is the most obvious, with an average monthly decrease of 12.51 yuan (P < 0.001). By age, the instantaneous change of CHD was the greatest for those older than 65 years old, with a decrease of 102.61 yuan (P = 0.030). CHD in 46–65 years old showed the most significant reduction, with an average monthly decline of 11.70 yuan (P < 0.01). BMIUE’s hypertension had the most considerable instantaneous change, which decreased 59.63 yuan (P = 0.010). BMIUE’s CHD showed the most apparent downward trend, with an average monthly decrease of 10.02 yuan (P = 0.010).ConclusionThe ITS analysis is an effective method of health policy evaluation. The implementation of the ZMDP can reduce the drug cost for chronic disease outpatients in the tertiary hospital and their economic burden. Follow-up policies still require targeted price adjustments in the health service system to adjust the drug cost-effectively.