OBJECTIVE: A literature search revealed a lack of information on how to treat patients who have failed to meet goal LDL level on statin therapy. The purpose of this retrospective, cohort study was to compare the cost-effectiveness of increasing the statin dose, changing to a different statin, adding an alternative therapy to the statin, changing to a different therapy, or not making any changes. METHODS: Medical charts of patients (n = 64) in a lipid clinic were utilized to gather patient demographics, CHD risk factors, treatment history, and laboratory values. Effectiveness was measured by whether the patient met goal LDL levels. Intervention costs included the cost of the medications, physician visits, and laboratory tests. RESULTS: The lowest total average cost occurred when the statin was changed to an alternative therapy ($96.39), followed by changing to a different statin ($131.40), increasing the statin dose ($134.69), making no change in therapy ($137.95), and adding an additional therapy to the statin ($153.03). The probability of a patient meeting LDL goal was highest when increasing the statin dose (0.406), followed by changing to a different statin (0.387), adding an additional therapy to the statin (0.320), not changing therapy (0.306), and changing the statin to an alternative therapy (0.111). The decision with the lowest average cost-effective ratio was increasing the statin dose ($331.75). Incremental analysis showed the cost of getting one more patient to goal was the lowest for changing to a different statin ($126.85), followed by increasing the statin dose ($173.16), and changing to an alternative therapy ($868.38). Sensitivity analysis found robust results for the probabilities of reaching goal. Cost data was sensitive between the decisions of increasing statin dose and changing statins. CONCLUSION: The most cost-effective decisions in this study were to increase the statin dose or change to a different statin.