OBJECTIVE Coronary heart disease (CHD) is increased two- to fourfold in subjects with NIDDM compared with normoglycemic subjects. This excess risk is only partially explained by conventional risk factors. We studied the effect of non-insulin-dependent diabetes mellitus (NIDDM) on the size of low-density lipoproteins (LDL). RESEARCH DESIGN AND METHODS We examined the effect of NIDDM on LDL size and subclass pattern B (LDL size < 253.5 Å) in 95 diabetic subjects and 371 nondiabetic subjects from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. RESULTS LDL size (Å) was significantly lower in diabetic subjects (men: 252.2 ± 1.8; women: 254.7 ± 1.3) than in nondiabetic subjects (men: 256.1 ± 0.8; women: 259.7 ± 0.7) (P = 0.007). After the use of analysis of covariance to adjust for triglyceride and high-density lipoprotein cholesterol, LDL size was still significantly lower in diabetic women than in nondiabetic women. In men, however, diabetes was no longer significantly associated with LDL size after similar adjustments. Fasting glucose was more strongly correlated with LDL size in women (r = −0.30) than in men (r = −0.18). CONCLUSIONS We conclude that LDL size is significantly lower in diabetic subjects of both sexes than in nondiabetic subjects, but that diabetic dyslipidemia accounts for the association in diabetic men. The stronger association between LDL size and diabetes in women than in men may partially explain the greater relative risk of CHD observed in women with NIDDM in some studies.