Patients with type 2 diabetes mellitus have an increased risk of cardiovascular events even when treated to low-density lipoprotein (LDL) cholesterol goals. The purpose of this study was to determine how many diabetic patients with low LDL cholesterol have correspondingly low numbers of LDL particles (LDL-P) and the extent to which those achieving target levels of LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol might still harbor residual risk associated with increased LDL-P. Split-sample measurements of LDL cholesterol, non-HDL cholesterol, and nuclear magnetic resonance measured LDL-P were performed on plasma samples from 2,355 patients with type 2 diabetes seen in clinical practice and who had LDL cholesterol levels <100 mg/dl. Substantial heterogeneity of LDL-P was noted among patients with low or very low levels of LDL cholesterol. Of 1,484 patients with low LDL cholesterol (70 to 99 mg/dl), only 385 (25.9%) had low levels of LDL-P (<20th percentile of an ethnically diverse contemporary reference population), whereas 468 (31.6%) had LDL-P values >50th percentile (>1,300 nmol/L). Among the 871 patients with very low LDL cholesterol, i.e., <70 mg/dl, 349 (40.1%) had LDL-P levels >1,000 nmol/L (>20th percentile) and 91 (10.4%) had LDL-P levels >50th percentile. For patients with high triglyceride values (200 to 400 mg/dl), there was less discordance between LDL-P and non-HDL cholesterol than between LDL-P and LDL cholesterol. However, for those with triglyceride levels <200 mg/dl, LDL-P distributions were similarly wide for patients having achieved low or very low targets of LDL cholesterol or non-HDL cholesterol. In conclusion, these data demonstrate that patients with type 2 diabetes mellitus and LDL cholesterol levels <100 mg/dl are extremely heterogeneous with regard to LDL-P and, by inference, LDL-based cardiovascular risk.