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Background: Since 2017, PERFORM2Scale, a research consortium with partners from seven countries in Africa and Europe, has steered the implementation and scale-up of a district-level health management strengthening intervention in Ghana, Malawi and Uganda. This article presents PERFORM2Scale's theory of change (ToC) and reflections upon and adaptations of the ToC over time. The article aims to contribute to understanding the benefits and challenges of using a ToC-based approach for monitoring and evaluating the scale-up of health system strengthening interventions, because there is limited documentation of this in the literature.Methods: The consortium held annual ToC reflections that entailed multiple participatory methods, including individual scoring exercises, country and consortium-wide group discussions and visualizations. The reflections were captured in detailed annual reports, on which this article is based.Results: The PERFORM2Scale ToC describes how the management strengthening intervention, which targets district health management teams, was expected to improve health workforce performance and service delivery at scale, and which assumptions were instrumental to track over time. The annual ToC reflections proved valuable in gaining a nuanced understanding of how change did (and did not) happen. This helped in strategizing on actions to further steer the scale-up the intervention. It also led to adaptations of the ToC over time. Based on the annual reflections, these actions and adaptations related to: assessing the scalability of the intervention, documentation and dissemination of evidence about the effects of the intervention, understanding power relationships between key stakeholders, the importance of developing and monitoring a scale-up strategy and identification of opportunities to integrate (parts of) the intervention into existing structures and strategies.Conclusions: PERFORM2Scale's experience provides lessons for using ToCs to monitor and evaluate the scale-up of health system strengthening interventions. ToCs can help in establishing a common vision on intervention scale-up. ToC-based approaches should include a variety of stakeholders and require their continued commitment to reflection and learning on intervention implementation and scale-up. ToC-based approaches can help in adapting interventions as well as scale-up processes to be in tune with contextual changes and stakeholders involved, to potentially increase chances for successful scale-up. [ABSTRACT FROM AUTHOR]