Background- Organizational and wider health system factors influence the implementation and success of interventions. Clinical Pathways in Acute Coronary Syndromes 2 is a cluster randomized trial of a clinical pathway-based intervention to improve acute coronary syndrome care in hospitals in China. We performed a qualitative evaluation to examine the system-level barriers to implementing clinical pathways in the dynamic healthcare environment of China. Methods and Results- A qualitative descriptive analysis of 40 in-depth interviews with health professionals conducted in a sample of 10 hospitals purposively selected to explore barriers to implementation of the intervention. Qualitative data were analyzed using the Framework method. In-depth interviews identified 5 key system-level barriers to effective implementation: (1) leadership support for implementing quality improvement, (2) variation in the capacity of clinical services and quality improvement resources, (3) fears of patient disputes and litigation, (4) healthcare funding constraints and high out-of-pocket expenses, and (5) patient-related factors. Conclusions- System-level barriers affect the ability of acute coronary syndrome clinical pathways to change practice. Addressing these barriers in the context of current and planned national health system reform will be critical for future improvements in the management of acute coronary syndromes, and potentially other hospitalized conditions, in China. Clinical Trial Registration- URL: http://www.anzctr.org.au/default.aspx. Register. Unique identifier: ACTRN12609000491268.