OBJECTIVES: AF is the most common chronic cardiac arrhythmia worldwide. Most patients with AF need life-long treatment to be protected from ischemic stroke. The aim was to conduct a high level cost assessment for stroke prevention and management in patients with AF [SPAF & SMAF] in 4 Latin American countries. METHODS: Overall the costs of SPAF & SMAF were determined through 59 face-to-face interviews with cardiologists in Argentina, Brazil, Chile and Venezuela. Treatment costs were estimated using benchmarks from major private and public hospitals in each country.  RESULTS: On average, the largest component of real-life medical expenditures for SPAF, under appropriate treatment given CHADS2 scores, was prescription drugs, which ranged from 68% in private to 75% in public. Annual SPAF treatment ranged in price from US$425 in Argentina to US$1,935 in Chile in private institutions and US$85 in Brazil to US$1,199 in Venezuela in public institutions. Moreover, overall treatment costs in Chile were 5X higher than the least expensive country in each sector.  For SMAF, using rivaroxaban vs the common Vitamin K antagonists resulted in a 24%-46% cost reduction for disease treatment at a national level due to better patient adherence.  This would decrease the stroke incidence/year, which would translate to US$143 M /yr in savings. CONCLUSIONS: AF is an important source of healthcare resource utilization because of repeated medical examinations, extensive use of laboratory tests and pharmacological treatments. Private and public institution cost differences are common in all 4 countries. Improving access to novel drugs, such as rivaroxaban, could help improve cost allocation, inducing a savings opportunity in each country.