Objective: The current study evaluated the appropriate utilization of ezetimibe add-on therapy to simvastatin and the cost-consequences based upon the following outcomes: ezetimibe response, LDL-C goal achievement, and switch to rosuvastatin. Methods: This was a retrospective review of VASDHS medical records to identify patients with active prescriptions for ezetimibe and simvastatin between January 1, 2004 and August 31, 2007. Base-case response was defined as =10% LDL-C reduction from baseline at study endpoint. Additional efficacy parameters included LDL-C goal achievement and switch to rosuvastatin if LDL-C goal not met. Pre-post analyses for continuous and binomial data were performed using Wilcoxon-ranked sum and McNemar's tests, respectively. Cost analyses were conducted from the payer perspective, utilizing total direct costs. Average cost-effectiveness ratios (CER) were calculated for (1) ezetimibe response, (2) LDL-C goal achievement, and (3) switch to rosuvastatin. Sensitivity analyses were performed varying the base-case response definition. Results: Overall, 121 patients met inclusion. Baseline characteristics were as follows: male 97.5%; Caucasian 78.5%; CHD 67.8%; diabetes 63.6%; symptomatic CAD 15.7%; PAD 18.2%; AAA 7.4%; >20% 10-year risk-score 95.9%; LDL-C goal <100 mg/dL 95.9%; LDL-C goal <70 mg/dL 57.9%; and smoker 28.1%. Pre-post comparisons showed significant differences from baseline LDL-C and cholesterol for both responders (p<0.001, p<0.001) and non-responders (p=0.028, p=0.028). Overall, 88.4% of patients responded to ezetimibe, while 36% of non-responders had their antilipemic regimen modified. In addition, 53% of patients reached LDL-C goal. Average CERs over a 9-month period using base-case response definition were: $1,705.64 per ezetimibe response, $2,054.26 per LDL-C goal achieved, and $2,997.56 per switch to rosuvastatin. Sensitivity analyses showed no change in trend for ezetimibe response, but changes were observed for the latter parameters. Conclusion: There is benefit in assessing both response rates as well as LDL-C goal attainment when determining a cost-analysis of ezetimibe add-on therapy to simvastatin.