Background: Anti-EGFR treatment of RAS wild-type metastatic colorectal cancer (mCRC) in Latin America includes cetuximab or panitumumab, added to chemotherapy (cet+CT and pan+CT, respectively). Adverse event (AE) profiles for each regimen may influence the treatment decision. This study aimed to estimate the associated financial impact of AE management in three countries: Argentina (AR), Brazil (BR) and Panama (PA) from a healthcare payer perspective. Methods: We revised a published Microsoft Excel-based economic model to calculate average patient- and population-level costs from a payer perspective of mCRC AE management for first-line cet+CT and pan+CT treatment, using AE frequency and severity data derived from the authorization relevant FDA prescribing information (PI), multiplied by the country-specific unit costs of managing AEs. Costs of AE management were obtained from publicly available sources in each country and converted to US dollars (USD). Country-specific market research data were applied to calculate costs at the eligible mCRC population level. The model structure and input parameters were endorsed by local practising oncologists. Results: A 17.5% (all-grade) and 31.6% (grade 3-4) lower average per patient AE frequency were estimated from the PI, for cet+CT vs pan+CT. Cost results are presented in the table. Projected AE management costs of cet+CT for the eligible mCRC population are $297,643 (AR), $124,981 (BR) and $65,895 (PA), annually, reducing current annual estimated AE costs by $42,181 (AR), $8,548 (BR) and $4,691 (PA). Conclusions: According to the average estimated AE frequencies, patients treated with cet+CT are expected to experience fewer AEs than with pan+CT. According to our analyses, the lower frequency rates could result in lower overall and severe AEs’ management costs, resulting in 12.4% (AR), 6.4% (BR) and 6.6% (PA) lower costs of AE management for cet+CT versus pan+CT.