Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipoprotein (HDL) and its subclasses. Our purpose in this post hoc subanalysis of an open-label study was to compare the effects of daily oral doses of rosuvastatin 40 mg with atorvastatin 80 mg over a 6-week period on direct LDL cholesterol and small dense LDL (sdLDL) cholesterol in 271 hyperlipidemic men and women versus baseline values. Rosuvastatin was significantly (p<0.01) more effective than atorvastatin in decreasing sdLDL cholesterol (-53% vs -46%), direct LDL cholesterol (-52% vs -50%), total cholesterol/HDL cholesterol ratio (-46% vs -39%), and non-HDL cholesterol (-51% vs -48%), The magnitude of these differences was modest, and the 2 statins caused similar decreases in triglyceride levels (-24% and -26%). In conclusion, our data indicate that the 2 statins, given at their maximal doses, significantly and beneficially alter the entire spectrum of lipoprotein particles, but that rosuvastatin is significantly more effective than atorvastatin in lowering direct LDL cholesterol and sdLDL cholesterol.