Background: The use of best practice guidelines (BPGs) has the potential to decrease the gap between best evidence and nursing and healthcare practices. We conducted an exploratory mixed method study to identify strategies, processes, and indicators relevant to the implementation and sustainability of two Registered Nurses’ Association of Ontario (RNAO) BPGs at Best Practice Spotlight Organizations® (BPSOs). Methods: Our study had four phases. In Phase 1, we triangulated two qualitative studies: a) secondary analysis of 126 narrative reports detailing implementation progress from 21 BPSOs spanning four sectors to identify strategies and processes used to support the implementation and sustainability of BPGs and b) interviews with 25 guideline implementers to identify additional strategies and processes. In Phase 2, we evaluated correlations between strategies and processes identified from the narrative reports and one process and one outcome indicator for each of the guideline. In Phase 3, the results from Phases 1 and 2 informed indicator development, led by an expert panel. In Phase 4, the indicators were assessed internally by RNAO staff and externally by Ontario Health Teams. A survey was used to validate proposed indicators to determine relevance, feasibility, readability, and usability with knowledge users and BPSO leaders. Results: Triangulation of the two qualitative studies revealed 46 codes of implementation and sustainability of BPGs, classified into eight overarching themes: Stakeholder Engagement, Practice Interventions, Capacity Building, Evidence-Based Culture, Leadership, Evaluation & Monitoring, Communication, and Governance. A total of 28 structure, process, or outcome indicators were developed. End users and BPSO leaders were agreeable with the indicators according to the validation survey.