OBJECTIVES:  To compare cost-effectiveness of rosuvastatin (RSV)  versus ezetimibe/simvastatin (E/S) in achieving LDL-C goals (NCEP-ATP III 2001 and 2004 guidelines), in daily outpatient practice in Mexico. METHODS: Retrospective study. From January 2004 to December 2010, outpatient medical records in 15 Mexican hospitals/clinics were reviewed to identify patients with dyslipidemia and their corresponding serum lipid measurements documented before receiving drug therapy with either RSV (5mg, 10mg, or 20mg once daily) or E/S (5/5mg, 10/10mg, 10/20mg or 10/40mg once daily); and lipid levels recorded at least after 8 weeks of treatment. The efficacy was assessed by a) the proportion of patients who achieved the LDL-C goal, and b) the percent reduction in LDL-C after 8 weeks of treatment. A cost-effectiveness analysis was performed from an institutional perspective, using the exchange rate of August 2011 of 12.2424 pesos/USD. RESULTS: Using ATP III 2001 criteria, percentage of patients who reached LDL-C goals was RSV: 81.3% and E/S 77.1% (p = 0.2972). Using ATP III 2004 criteria were: RSV, 61.3% vs. E/S, 58.5% (p=0.2548). The average treatment cost was statistically significant higher for E/S patients (239.49 USD) versus 192.74 USD for RSV patients (p=0.0033). The cost of 1% reduction in LDL-C was RSV: 4.69 USD and E/S: 7.13 USD. Cost per patient treated to ATP-III goal 2001 criteria was: RSV, 219.5 USD versus E/S, 306.0 USD and treated to ATP-III goal 2004 criteria was: RSV, 282.2 versus E/S, 459.1 USD. The overall incidence rate of adverse events was E/S: 19.5% versus RSV: 15.3%. The percentage of patients reporting moderate or severe adverse events was E/S: 6.8% and RSV: 4.7%. CONCLUSIONS: According to this exploratory, non-controlled retrospective study, in daily clinical practice in Mexican dyslipidemic patients, treatment with RSV has similar efficacy and safety, but it is more cost-effectiveness than E/S in reaching cholesterol goals.