© 2018 John Wiley & Sons, Ltd. Rationale, aims, and objectives: Underuse of anticoagulants in atrial fibrillation is known to increase the risk of stroke and is an international problem. The National Institute for Health Care and Excellence guidance CG180 seeks to reduce atrial fibrillation related strokes through prescriptions of Non-vitamin K antagonist Oral Anticoagulants. A quality improvement programme was established by the West of England Academic Health Science Network (West of England AHSN) to implement this guidance into General Practice. A realist evaluation identified whether the quality improvement programme worked, determining how and in what circumstances. Methods: Six General Practices in 1 region, became the case study sites. Quality improvement team, doctor, and pharmacist meetings within each of the General Practices were recorded at 3 stages: initial planning, review, and final. Additionally, 15 interviews conducted with the practice leads explored experiences of the quality improvement process. Observation and interview data were analysed and compared against the initial programme theory. Results: The quality improvement resources available were used variably, with the training being valued by all. The initial programme theories were refined. In particular, local workload pressures and individual General Practitioner experiences and pre-conceived ideas were acknowledged. Where key motivators were in place, such as prior experience, the programme achieved optimal outcomes and secured a lasting quality improvement legacy. Conclusion: The employment of a quality improvement programme can deliver practice change and improvement legacy outcomes when particular mechanisms are employed and in contexts where there is a commitment to improve service.