ObjectivesThis study aimed to estimate the budget impact of adopting direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation in Malawi after the inclusion of DOACs in the World Health Organization’s essential medicine list. MethodsA model was developed in Microsoft Excel. An eligible population of 201 491 was adjusted with 0.05 % incidence rate and mortality rates yearly according to the treatments. The model estimated the implication of supplementing rivaroxaban or apixaban to the standard treatment mix (also the comparator), thus warfarin and aspirin. The current market share of 43% aspirin and 57% warfarin was adjusted proportionally with 10% DOAC uptake in the first year and 5% annually over the subsequent 4 years. Clinical events of stroke and major bleeding from the ROCKET-AF and ARISTOTLE trials were used because health outcome indicators affect resource utilization. The analysis was conducted solely from the Malawi Ministry of Health perspective and it considered direct costs over 5 years. The sensitivity analysis involved varying drug costs, population, and care costs from both public and private sectors. ResultsThe research suggests that despite potential savings of $6 644 141 to $6 930 812 in stroke care because of fewer stroke events, the total Ministry of Health healthcare budget (approximately $260 400 000) may increase by between $42 488 342 to $101 633 644 in 5 years because drug acquisition costs are greater than savings. ConclusionsWith a fixed budget and current DOACs prices, Malawi can consider using DOACs in patients at the highest risk while waiting for cheaper generic versions.