Hypertriglyceridemia, which often leads to both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolic disorders, is a strong risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). We hypothesized that the triglyceride (TG)/HDL cholesterol (TG/HDL-C) ratio may be more useful for estimation of the LDL-particle size, as a well-known risk factor for ASCVD, as compared to the serum TG level per se. Polyacrylamide gel electrophoresis was used in this study to estimate the LDL-particle size [relative LDL migration (LDL-Rm value)] in 649 consecutive patients with one additional risk factor for ASCVD. Multivariable regression analysis identified both serum TG (β = 0.556, p < 0.0001) and the serum TG/HDL-C ratio (β = 0.607, p < 0.0001) as independent indicators of the LDL-particle size. In terms of evaluation of the accuracy of indicators of LDL-Rm values equal to or greater than 0.40, which are suggestive of the presence of large amounts of small-dense LDL and represent the upper limit (mean + 2 standard deviation) of the normal range in this population, both the serum TG level and serum TG/HDL-C ratio showed high accurate areas under the receiver-operating characteristic curve (0.900 vs. 0.914), but with a negative likelihood ratio of 0.506 vs. 0.039, indicating that the TG/HDL-C ratio model is superior for excluding patients with values below the cutoff value and with LDL-Rm values ≥ 0.40. Furthermore, in 456 patients followed up for at least 1 year, multivariable regression analysis identified increased serum TG/HDL-C ratio as an independent predictor of a decreased LDL-particle size. These results suggest that the serum TG/HDL-C ratio may be more useful for assessing the risk of ASCVD as compared to the serum TG level per se. To reduce the risk of ASCVD, it may be important to focus not only on changes of the serum LDL-C, but also on those of the serum TG/HDL-C ratio.