Objective: The purpose of this analysis was to study the effectiveness and cost-effectiveness of oral rosuvastatin (RSV) 10 mg/day vs. oral ezetimibe/simvastatin (E/S) 10/20 mg/day in patients who met the LDL-C goals set out in the National Cholesterol Education Program (NCEP), Adult Treatment Panel III (ATP III) 2001 and 2004 guidelines, and the percent change in the atherogenic lipid profile in daily outpatient practice in a high specialty Hospital in Mexico City. Methods: From January 2004 to December 2005, outpatient medical records in the Cardiology Service were reviewed according to the following criteria: established dyslipidemia diagnosis, triglycerides and serum lipid measurements (TC, LDL-C, HDL-C) taken before receiving drug therapy with either oral RSV 10 mg/day or oral E/S 10/20 mg/day once daily, no other related lipid-lowering treatment administered, and lipid levels recorded at 8 weeks of treatment. A cost analysis was performed from an institutional perspective, using the exchange rate as of October 2006 of 10.9007 pesos / US dollar. A deterministic analysis was performed comparing treatment costs, proportion of patients achieving the ATP III goal, and the percentage decrease in LDL-C. In addition, a stochastic analysis was performed, considering the uncertainty around the estimations for mean cost and mean effectiveness estimations. Results: Using the ATP III 2001 criteria, the percentage of patients who reached the LDL-C goals was 81.4% for patients who received RSV, while the proportion for patients who received E/S was 58.4% (p < 0.001). Results according to the ATP III 2004 criteria were: RSV, 46.4% vs. E/S, 31.4% (p = 0.04). The cost of a 1% reduction in LDL-C was $2.02 with RSV and $4.09 with E/S. The cost-effectiveness acceptability curve showed that RSV might be more cost-effective than E/S, based on patients who achieved the 2004 goals. Conclusions: According to this exploratory, non-controlled retrospective analysis, it can be said that in daily clinical practice in high-cardiovascular-risk Mexican patients, treatment with oral RSV 10 mg/day is more effective and less costly than treatment with the fixed-combination oral E/S 10/20 mg/day.