BACKGROUND.  Atrial fibrillation (AF) is associated with development of thromboembolic events [1]. The standard therapy used in patients with non-valvular atrial fibrillation (NVAF) with risk of stroke is Warfarin. There are new oral anticoagulants (NOACs) that also are recommended [2].OBJECTIVES:   Evaluate cost-effectiveness of Apixaban compared to Oral Anticoagulants in the prevention of thromboembolitic events in NVAF patients from perspective of Guatemala’s Public HealthCare System (IGSS). METHODS: A Markov decision-analysis model was designed using data from clinical trials [3,4,5] (indirect comparisons, where appropriate) to evaluate lifetime costs and quality-adjusted life-years (QALY) of Apixaban (5mgBID) in comparison to Rivaroxaban (20mg/day) and Warfarin (5mg/day). IGSS used Warfarin and Rivaroxaban in NVAF patients. The health states evaluated were: ischemic and hemorrhagic strokes, hemorrhagic events (intracranial hemorrhage, other major bleeds and clinically relevant non major bleeds), systemic embolism (SE) and myocardial infarction (MI). The model population was a hypothetical cohort of 70-year-old NVAF patients, suitable to Vitamin K antagonist treatment. Only direct medical costs were considerate and taken from IGSS databases from 2014 [6,7]. Outcomes were: overall cost, QALY and ICER.  Cost and health outcomes were discounted at 5.0% per year, using a lifetime horizon. RESULTS:   Apixaban is the only therapy that prevents and improved all clinical outcomes. Apixaban prevented: 3 Ischemic Strokes, 14 hemorrhagic strokes, 71 hemorrhagic events, 1 MI and 3 SE in comparison to Warfarin.  Overall costs in a lifetime period per patient were US$9,190; US$11,763; US$12,045 for Warfarin, Apixaban, and Rivaroxaban respectively.  Apixaban earned the highest QALY 5.740; Rivaroxaban reported 5.699 and Warfarin 5.570. Used Warfarin as a base, the ICER of Apixaban and Rivaroxaban were US$15,135 and US$21,961 respectively. CONCLUSIONS: Neither Apixaban nor Rivaroxaban are Cost-Effectiveness therapies in comparison with Warfarin according Guatemala’s 3GPB (US$10,400). Among the NOACs currently used by IGSS, Apixaban is shown to be a cost-saving therapy in comparison to Rivaroxaban.