OBJECTIVES:   The economic burden of atrial fibrillation (AF) in the Latin American region has not been previously quantified. This research assessed the economic burden of AF in Brazil, Chile, Colombia, Ecuador, El Salvador, Mexico, Panama, Peru, Venezuela. METHODS:  To estimate the cost of AF by country, a prevalence approach was used. Costs were estimated for the year 2015 and included health system expenditures, productivity losses (absenteeism, lower workforce participation, premature mortality) and informal care costs, and deadweight losses associated with government expenditures. Data inputs for costs, including prevalence and mortality were based on secondary data sources informed by a targeted literature review including country specific grey literature and data sources. The study also appraised the value of the loss of healthy life, measured in disability adjusted life years (DALYs), using global burden of disease disability weights. RESULTS:  AF was found to affect approximately 2.7 million people (0.8% of the adult population, average of 69.5 years old) in selected Latin American countries in 2015. This leads to significant wellbeing loss, estimated at 664,460 DALYs, and economic burden, estimated at USD2.4 billion in 2015. Health system expenditures accounted for USD2.3billion (95%) and productivity costs USD115million (5%) of the total financial burden of AF. On average, health system expenditure represented 0.06% of total gross domestic product (GDP) across the nine countries with Brazil (0.07%), Chile (0.08%), Colombia (0.07%), Ecuador (0.06%) and El Salvador (0.13%) spending more than the average. Total financial costs averaged 0.06% of GDP. CONCLUSIONS:   AF imposes a significant burden to the health system and society in Latin America. Health system expenditure accounts for the majority of the burden of AF in the region. Prevention and appropriate management of AF may result in substantial wellbeing benefits and economic savings.