Emerging evidence from large observational studies and causal genetic studies suggest that elevated very-low-density lipoproteins (VLDL) are important and independent risk factors for atherosclerosis, myocardial infarction, and coronary artery disease. The cholesterol content of VLDL particles is often combined as overall remnant cholesterol; however, VLDL particles encompasses a heterogeneous group of lipoproteins that vary significantly in size, density, and structural composition, contributing to metabolic heterogeneity of VLDL particles. This heterogeneity has been suggested important for understanding the atherogenicity of VLDL particles. Nevertheless, remnant cholesterol lack precision to capture metabolic heterogeneity of VLDL subfractions; in contrast, advanced techniques such as nuclear magnetic resonance (NMR) spectroscopy provide more accurate estimates of VLDL particle number and cholesterol content across subfractions. This review aims at summarizing current evidence of the association between remnant cholesterol and particle number of VLDL subfractions as risk factors for myocardial infarction and coronary artery disease including pros and cons for using easily accessible remnant cholesterol versus using more advanced measurement methods for estimation of particle number of VLDL subfractions.