Lipoprotein subclass measurements may enhance the prediction of coronary artery disease (CAD) risk, but clinical application of such information has been hindered by the relatively laborious and time-consuming nature of laboratory measurement methods. In this study, lipoprotein subclass analyses were performed on frozen plasma samples from 241 participants in the Pravastatin Limitation of Atherosclerosis in the Coronary arteries Trial using an automated nuclear magnetic resonance technique. The objective was to determine if levels of these subclasses provided additional information on the progression of CAD, based on the change in the minimum lumen diameter, over a 3-year period. After adjustment for race, sex, age, treatment group, baseline lumen diameter, and chemically measured levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol, on-trial predictors (p <0.05) of progression included an elevated LDL particle number, and levels of small LDL and small HDL. Within treatment groups, CAD progression was most strongly related to the LDL particle number (placebo) and levels of small HDL (pravastatin). In logistic regression models that adjusted for chemically determined lipid levels and other covariates, a small LDL level > or = 30 mg/dl (median) was associated with a ninefold increased risk of CAD progression (p <0.01) in the placebo group. These results indicate that levels of various lipoprotein subclasses may provide useful information on CAD risk even if levels of traditional risk factors are known.