Background <p>The eleventh version of ICD (ICD-11) is the latest version of ICD adopted by the 72nd World Health Assembly in 2019. Worldwide, countries are piloting the ICD-11 and conducting relevant feasibility studies. ICD-11 implementation was not a straightforward initiative, requiring the involvement of various stakeholders. The challenges and facilitators beyond the pilot implementation settings were less well understood. There is a need to understand the perspective of implementers who have experienced ICD-11 implementation involving heterogeneous systems.</p> Methods <p>We used primary data gathered between April and May 2024 via semi-structured interviews with the implementers (<i>n</i> = 15) who were members of Malaysia’s national-level ICD-11 implementation committee. We collected and analyzed the qualitative data using the Consolidated Framework for Implementation Research (CFIR) 2022 to understand how the key informants implemented ICD-11. Permission was obtained to record the interviews, which were transcribed and coded using NVivo 12. We used conventional qualitative content analysis to identify key facilitators and challenges to ICD-11 implementation.</p> Results <p>By applying CFIR 2022, we determined the relevant factors influencing the implementation of ICD-11 in Malaysia. Defining the facilitators and challenges provided direction on areas of focus and improvement in the ICD-11 implementation context. The facilitators included the lead organizations’ reputation, fulfilment of existing use case, extensive content with terminology service, trialability, lower cost, collaboration with external agencies, improvement of existing laws, clear roles within the organization, effective communication, emerging needs, suitability with existing workflow, easy access to knowledge, motivated team, availability of existing frameworks, and engaging team. The challenges were ICD-11’s complexity, customization, support by top management, vendor’s steep learning curve, inadequate documentation, outdated infrastructure, data duplication and validity, workforce, impact on work processes, funding, and technical expertise.</p> Conclusions <p>This study identified key facilitators and challenges in nationwide ICD-11 adoption, providing critical insights for implementation across heterogeneous systems. Successful adoption requires addressing coding, technical and policy aspects. Future research should evaluate user perspectives and the adaptability of implementation strategies in diverse settings.</p> Clinical trial number <p>Not applicable.</p>