OBJECTIVE: To compare the effectiveness and cost-effectiveness among generic and branded statins in routine clinical practice. METHODS: Retrospective database study of patients, 18+, who were newly prescribed statin therapy. Statin effectiveness and cost-effectiveness in reducing low-density lipoprotein cholesterol (LDL-C) and attaining LDL-C goals were evaluated. RESULTS: Of 10,421 eligible patients, % LDL-C reduction was significantly greater (P < 0.001) with rosuvastatin (-31.6%) than other statins (-13.9 to -21.9%). Percentage of patients at moderate/high risk attaining LDL-C goal was higher (P < 0.001) for rosuvastatin (76.1%) versus other statins (57.6-72.6%). Rosuvastatin was more effective and less costly than atorvastatin. Among generic statins, simvastatin required >61% discount to branded price to achieve similar cost-effectiveness as generic lovastatin. CONCLUSIONS: In clinical practice, rosuvastatin is more effective and less costly in lowering LDL-C and LDL-C goal attainment compared with atorvastatin. Simvastatin was more cost-effective compared with lovastatin if >61% discount to branded price was achieved.