BACKGROUND: Latin America has witnessed a marked increase in cardiovascular (CV) disease, the leading cause of death in many countries. The benefits of lipid-lowering therapy to reduce CV-related events are widely accepted. Clinical evidence suggests that rosuvastatin is associated with slightly greater reductions in low-density lipoprotein cholesterol levels than is atorvastatin at comparable doses. Rosuvastatin, however, is often priced at a premium. OBJECTIVE: Our objective was to examine the cost-effectiveness of using atorvastatin versus rosuvastatin in reducing CV events in Brazil and Colombia using real-world prices. METHODS: A global Markov cohort model of primary and secondary CV prevention was developed and adapted to Brazilian and Colombian settings. The risks and costs of major CV events and efficacy, adherence, and costs of statins were considered. Total gains in life-years, quality-adjusted life-years, major CV events avoided, and costs over the lifetime horizon were estimated. Several dose comparisons were considered. RESULTS: In the Colombian analyses, differences in drug costs between therapies were considerable while outcomes were similar. The incremental cost per quality-adjusted life-year gained for rosuvastatin versus atorvastatin was more than $700,000 and $200,000 in primary and secondary prevention, respectively. Brazilian analyses found lower incremental cost-effectiveness ratios for rosuvastatin at some dose comparisons due to similar pricing between statins. Sensitivity analyses revealed that changes in treatment efficacy and adherence had the largest impact on results. CONCLUSIONS: In primary and secondary CV prevention, the efficacy advantage of rosuvastatin was minimal, while its acquisition cost was higher, particularly in Colombia. The incremental cost-effectiveness ratios were, therefore, generally in favor of atorvastatin being the cost-effective option.