Yes / Objective: To better understand the factors influencing the uptake of direct oral anticoagulants (DOACs) across different health economies in National Health Service England from the perspective of health professionals and other health economy stakeholders. Design: Qualitative interview study using a critical realism perspective and informed by the Diffusion of Innovations in Service Organisations model. Setting: Three health economies in the North of England, United Kingdom. Participants: Healthcare professionals involved in the management of patients requiring oral anticoagulants, stakeholders involved in the implementation of DOACs and representatives of pharmaceutical industry companies and patient support groups. Intervention: Semistructured interviews (face-to-face or telephone) were conducted with 46 participants. Interviews were analysed using the Framework method. Results: Identified factors having an impact on the uptake of DOACs were grouped into four themes: perceived value of the innovation, clinician practice environment, local health economy readiness for change, and the external health service context. Together, these factors influenced what therapy options were offered and prescribed to patients with atrial fibrillation. The interviews also highlighted strategies used to improve or restrict the uptake of DOACs and tensions between providing patient-centred care and managing financial implications for commissioners. Conclusions: The findings contribute to the wider literature by providing a new and in-depth understanding on the uptake of DOACs. The findings may be applicable to other new medicines used in chronic health conditions. / This work presents research funded by the Pharmacy Research UK (grant number: PRUK-2018-GA-1-KM) and Leeds Teaching Hospitals NHS Trust (grant number: N/A).