Many patient safety initiatives fail to be adopted and implemented, even when proven effective. This creates the well-recognized know-do gap, referring to the discrepancy between what healthcare workers know should be done based on evidence and what takes place in practice. We aimed to develop a framework to improve the adoption and implementation of patient safety initiatives. We conducted a background literature review followed by qualitative interviews with patient safety leaders to identify barriers and facilitators to adoption and implementation. Inductive thematic analysis was used to generate themes that informed the development of the framework. We used a consensus-building approach to co-create the framework and guidance tool with an Ad Hoc Committee made up of subject-matter experts and patient family advisors. The framework was tested for utility, feasibility, and acceptability through qualitative interviews. The Patient Safety Adoption Framework contains 5 domains and 6 subdomains. The domains are leadership (subdomains: prioritization, accountability, governance), culture and context, process (subdomains: co-creation, high reliability, engagement), meaningful measurement, and person-centeredness. A guidance tool was developed to provide practical guidance for improvement teams using the framework. Testing affirmed the framework and guidance tool with a high degree of acceptability, feasibility, and utility among implementers and subject-matter experts. The Patient Safety Adoption Framework provides the essential components necessary to facilitate the adoption and implementation of patient safety initiatives. The framework offers a roadmap for healthcare organizations striving to close the know-do gap.