Health care payers have become increasingly interested in economic analyses to guide the allocation of limited health care resources. The Surrogate Marker Cost-Efficacy (SMaC) study was undertaken to assess the economics of treatment with simvastatin versus treatment with atorvastatin in reducing low-density lipoprotein cholesterol (LDL-C) in patients in 10 European countries, based on the results of a 1-year, double-blind, parallel-group clinical trial. Participants were between 18 and 80 years of age (n = 177; median age, 57; 94 men and 83 women). Entry criteria were a baseline LDL-C value between 4.2 and 7.8 mmol/L (160 to 300 mg/dL) and a triglyceride value < or =4.5 mmol/L (400 mg/dL). Patients were randomly assigned to receive simvastatin 10 mg or atorvastatin 10 mg. At 16 weeks, any patients not reaching their appropriate LDL-C level received simvastatin 20 mg/d or atorvastatin 20 mg/d. Patients were then followed up for a total of 52 weeks. The overall euro cost analysis was based on the weighted average price of each product across all the independent pharmaceutical markets based on official euro conversion rates. Individual country analyses also were conducted in each local currency. Over the 52-week study, there were no significant differences in the percentage of patients achieving an appropriate LDL-C level (simvastatin 48%, atorvastatin 50%). In the overall euro cost analysis, the cumulative cost of atorvastatin (134 euros) was 33% more than for simvastatin (101 euros) during the first 16 weeks. After titration to 20 mg, the total cost of treatment during the 52-week study remained significantly lower in the simvastatin group than in the atorvastatin group (429 vs 538 euros; P<0.0001). In individual country analyses, therapy with simvastatin was significantly less expensive than therapy with atorvastatin in 8 of 10 countries (P = 0.001 to 0.003). In the remaining 2 countries, there was no significant difference in cost. Across the countries included in the evaluation, there was a significant reduction in the cost of getting patients to appropriate LDL-C levels with simvastatin compared with atorvastatin. These results should provide useful information for physicians and payers; however, additional long-term clinical trials are required to assess fully how treatment with atorvastatin affects patient outcomes, safety, and costs.