OBJECTIVE: To estimate the comparative cost-effectiveness of atorvastatin and simvastatin. METHODS: A randomized clinical trial set in general practice. Effectiveness was measured by percentage reduction in total cholesterol and percentage of patients achieving NHF targets. The costs calculated in the study were hospital admissions, emergency room/clinic visits, visits to GPs and specialists, tests/investigations, treatment of adverse events and drug costs. RESULTS: Of the 691 patients in the atorvastatin arm, 682 used healthcare resources. Of the 337 patients in the simvastatin arm, 332 used healthcare resources. The monthly drug costs with atorvastatin was $48.30 for 10mg, $66.93 for 20mg, with simvastatin at $42.06 for 10 mg, $58.12 for 20mg. The average cost of healthcare for atorvastatin and simvastatin was $460.48 and $490.11 respectively (p=0.47). Adverse events accounted for 60% of all healthcare costs in the atorvastatin group, 77% in the simvastatin group. The weighted average monthly drug costs (WAMDC) after 6 weeks of treatment were $48.30 for atorvastatin and $42.06 for simvastatin. 38% of patients reached NHF target cholesterol levels on atorvastatin, 25.5% on simvastatin. The cost per responder was $1.27 with atorvastatin, $1.63 with simvastatin. After 12 weeks of treatment the WAMDC was $59.53 for atorvastatin, $53.77 for simvastatin with 47.5% and 33.8% response rates, respectively. The incremental cost-effectiveness of an extra patient achieving target on atorvastatin was $0.50 at 6 weeks, $0.42 at 12 weeks, $0.26 at 18 weeks and $0.51 at 24 weeks. CONCLUSION: Atorvastatin achieved a greater percentage reduction in total cholesterol per mg than simvastatin, and was equally well tolerated. While drug costs for atorvastatin were slightly higher, overall healthcare costs were lower than for simvastatin. Atorvastatin was more cost-effective than simvastatin in achieving NHF targets. The incremental cost-effectiveness of atorvastatin suggests additional patients can achieve NHF targets relatively inexpensively. (2,3 on behalf of the AAA study group)