OBJECTIVE To present data from the Cholesterol Lowering Atherosclerosis Study (CLAS) and the Monitored Atherosclerosis Regression Study (MARS) demonstrating the relationship between triglyceride-rich lipoproteins and progression of atherosclerosis. RESULTS CLAS and MARS were randomized, placebo-controlled, arterial imaging trials designed to determine the effects of lipid lowering on the progress of atherosclerosis using coronary angiographic and carotid arterial wall intima-media thickness measurement end points. Included in each of these trials were specific measurements of triglyceride-rich lipoproteins in addition to the traditional lipid measurements. CONCLUSIONS CLAS and MARS indicate that specific triglyceride-rich lipoproteins such as VLDL, IDL, apolipoprotein B-containing lipoprotein particles (i.e. lipoprotein Bc), and markers of triglyceride-rich lipoprotein metabolism (i.e. apolipoprotein C-III) are significantly related to progression of atherosclerosis. These specific triglyceride-rich lipoproteins are associated with the progression of atherosclerosis independently of HDL cholesterol levels. Importantly, there appears to be a differential effect of triglyceride-rich lipoproteins and cholesteryl-ester rich lipoproteins (i.e. LDL cholesterol) on the progression of mild/moderate and severe coronary artery lesions, respectively. This association not only suggests that certain risk factors may act early and others late in the athersclerotic process, but that triglyceride-rich lipoproteins are associated with progression of the lesions (mild/moderate lesions) which are predominantly responsible for clinical coronary events.