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Objective Secondary prevention strategies for coronary heart disease (CHD) can play a crucial role in averting acute coronary events and enhancing the overall well-being of CHD patients. This study aimed to investigate the knowledge, attitude and practice (KAP) of CHD patients in Shandong Province, China, toward secondary prevention medication regimens for CHD.Design A multi-centre cross-sectional study.Setting Using a self-administered questionnaire.Participants This survey was conducted between October 2023 and February 2024 across four tertiary hospitals in Shandong Province, including the Provincial Hospital Affiliated with Shandong First Medical University, Qilu Hospital of Shandong University, Jinan Central Hospital and Jinan Fourth People’s Hospital.Primary and secondary outcome measures The KAP of CHD patients toward secondary prevention medication regimens.Results A total of 495 participants were finally enrolled, 347 (70.1%) were male and 248 (50.1%) were aged greater than or equal to 65 years. The mean score of KAP was 6.73 (5.19) (range: 0–20), 29.15 (3.81) (range: 7–35) and 28.61 (3.90) (range: 7–35), respectively. The structural equation model demonstrated that knowledge had a direct effect on attitude (β=0.427, p<0.001) and attitude had a direct effect on practice (β=0.571, p<0.001). In addition, the direct impact of knowledge had an indirect impact on practice through attitude (β=0.244, p<0.001).Conclusions CHD patients demonstrated insufficient knowledge, positive attitude and proactive practice toward secondary prevention medication regimens for CHD. It is recommended that healthcare providers implement targeted educational interventions to enhance patients’ knowledge levels regarding secondary prevention medication regimens for CHD.