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Introduction Improving the quality of self-management support (SMS) for treatment-related toxicities is a priority in cancer care. Successful implementation of SMS programmes depends on tailoring implementation strategies to organisational readiness factors and barriers/enablers, however, a systematic process for this is lacking. In this formative phase of our implementation-effectiveness trial, Self-Management and Activation to Reduce Treatment-Related Toxicities, we evaluated readiness based on constructs in the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT) and developed a process for mapping implementation strategies to local contexts. Methods In this convergent mixed-method study, surveys and interviews were used to assess readiness and barriers/enablers for SMS among stakeholders in 3 disease site groups at 3 regional cancer centres (RCCs) in Ontario, Canada. Median survey responses were classified as a barrier, enabler or neutral based on a priori cut-off values. Barriers/enablers at each centre were mapped to CFIR and then inputted into the CFIR-Expert Recommendations for Implementing Change Strategy Matching Tool V.1.0 (CFIR-ERIC) to identify centrespecific implementation strategies. Qualitative data were separately analysed and themes mapped to CFIR constructs to provide a deeper understanding of barriers/enablers. Results SMS in most of the RCCs was not systematically delivered, yet most stakeholders (n=78; respondent rate=50%) valued SMS. For centre 1, 7 barriers/12 enablers were identified, 14 barriers/9 enablers for centre 2 and 11 barriers/5 enablers for centre 3. Of the total 46 strategies identified, 30 (65%) were common across centres as core implementation strategies and 5 tailored implementation recommendations were identified for centres 1 and 3, and 4 for centre 2. Conclusions The CFIR and CFIR-ERIC were valuable tools for tailoring SMS implementation to readiness and barriers/enablers, whereas NPT helped to clarify the clinical work of implementation. Our approach to tailoring of implementation strategies may have relevance for other studies. [ABSTRACT FROM AUTHOR]