Background Stroke prevention is central to the management of atrial fibrillation (AF), but there remains a residual risk of adverse outcomes in anticoagulated AF patients. Hence, current guidelines have proposed a more holistic or integrated approach to AF management, based on the Atrial fibrillation Better Care (ABC) pathway, as follows: (A) avoid stroke with anticoagulation; (B) better symptom control with patient-centred symptom directed decisions on rate or rhythm control; and (C) cardiovascular and comorbidity management, including lifestyle factors. There has been no formal healthcare cost analysis from the UK National Health Service (NHS) perspective of ABC pathway implementation to optimize the management of AF. Our aim was to estimate the number of patients with AF in the UK each year up to 2040, their morbidity and mortality, and the associated healthcare costs, and secondly, to estimate improvements in morbidity and mortality of implementing an ABC pathway, and the impact on costs.Results In 2020, there were an estimated 1 463 538 AF patients, resulting in 286 pound million of stroke care and 191 pound million of care related to bleeds annually. By 2030, it is expected that there will be 2 115 332 AF patients, resulting in 666 pound million of stroke healthcare and 444 pound million of healthcare related to bleeds. By 2040, this is expected to rise to 2 856 489 AF patients, with 1096 pound million of stroke healthcare and 731 pound million of healthcare related to bleeds for that year. If in 2040 patients are managed on an ABC pathway, this could prevent between 3724 and 18 622 strokes and between 5378 and 26 890 bleeds, and save between 16 131 and 80 653 lives depending on the proportion of patients managed on the pathway. This would equate to cost reductions of between 143.9 pound million and 719.6 pound million for the year.Conclusion We estimate that there will be a substantial healthcare burden in the UK NHS associated with AF, from strokes, bleeds, and mortality over the next decades. If patients are managed with a holistic or integrated care approach based on the ABC pathway, this could prevent strokes and bleeds that equate to substantial NHS healthcare cost reductions, and save lives.