OBJECTIVES: Rheumatoid arthritis (RA), an autoimmune condition, and osteoarthritis (OA), a degenerative joint disorder, are both associated with inflammatory reactions. Pain relievers could ameliorate this economic burden; however depending on the first-line treatment chosen they could raise the likelihood of gastrointestinal (GI) complications or cardiovascular (CV) events. The aim of this study is to calculate the direct and indirect costs of GI and CV events associated with common pain relievers for RA and OA patients in Brazil, Mexico, Colombia, Argentina and Costa Rica from the public payer’s perspective. METHODS: Resource use and medical cost data was collected in 2011 from local official databases and public hospital records from each noted LA market (all costs are expressed in 2012 US$). Events considered in this assessment were: dyspepsia, symptomatic ulcer, major bleedings (severe GI complication), myocardial infarction, ischemic stroke and heart failure. Direct medical costs considered were: outpatient visits, inpatient costs, lab and diagnostic tests, acquisition drug costs, concomitant medication, and emergency room services. To estimate indirect costs, human capital approach was considered involving productivity losses based in average wages for each LA market. RESULTS: Among LA countries, Brazil showed the highest overall adverse event cost per patient with dyspepsia (US$97.10) and Costa Rica the lowest (US$57.00). In addition, a symptomatic ulcer cost ranged between US$933.00 - US$705.60; major bleeding (US$6,807.30 - US$4,960.40); myocardial infarction (US$13,330.30 - US$7916.70); ischemic stroke (US$6,427.20 - US$3125.00) and heart failure (US$7,221.70 - US$4,152.80). In average, Brazilian and Mexican overall costs were among the highest, as opposed to Argentina and Costa Rica which were among the countries with lowest costs. Indirect costs followed the same trend (less than 15% of total direct costs). CONCLUSIONS: Unexpected event costs associated with pain relievers could raise the economic burden of OA and RA significantly in LA. Thus, these findings could help decision makers to identify cost-effective pain therapies in markets where this cost data is unavailable.