Background: Increased life expectancy is associated with an increase in the burden of chronic cardiovascular disease. Objective: To assess the efficacy and safety of high-dose atorvastatin in patients 65 years of age or older. Design: A prespecified secondary analysis of the Treating to New Targets study, a randomized, double-blind clinical trial. Setting: 256 sites in 14 countries participating in the Treating to New Targets study. Participants: 10 001 patients (3809 patients ≥65 years of age) with coronary heart disease (CHD) and low-density lipoprotein cholesterol levels less than 3.4 mmol/L (<130 mg/dL). Intervention: Patients were randomly assigned to receive atorvastatin, 10 or 80 mg/d. Measurements: The primary end point was the occurrence of a first major cardiovascular event (death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke). Results: In patients 65 years of age or older, absolute risk was reduced by 2.3% and relative risk by 19% for major cardiovascular events in favor of the high-dose atorvastatin group (hazard ratio, 0.81 [95% CI, 0.67 to 0.98]; P = 0.032). Among the components of the composite outcome, the mortality rates from CHD, nonfatal non-procedure-related myocardial infarction, and fatal or nonfatal stroke (ischemic, embolic, hemorrhagic, or unknown origin) were all lower in older patients who received high-dose atorvastatin, although the difference was not statistically significant for each individual component. The improved clinical outcome in patients 65 years of age or older was not associated with persistent elevations in creatine kinase levels. Limitation: Because the study was a secondary analysis, the findings should be interpreted within the context of the main study results. Conclusions: The analysis suggests that additional clinical benefit can be achieved by treating older patients with CHD more aggressively to reduce low-density lipoprotein cholesterol levels to less than 2.6 mmol/L (<100 mg/dL). The findings support the use of intensive low-density lipoprotein cholesterol-lowering therapy in high-risk older persons with established cardiovascular disease. © 2007 American College of Physicians.