Background: Limited data suggest that the effects of abdominal subcutaneous adipose tissue (SAT) on cardiovascular disease risk may depend on accompanying amounts of abdominal visceral adipose tissue (VAT). Objective: The objective was to examine whether abdominal VAT area modifies the effects of abdominal SAT area on subclinical atherosclerosis and cardiometabolic risk factors in both whites and African Americans. Design: Computed tomographic measures of abdominal SAT and VAT were examined in relation to carotid intima-media thickness (cIMT) and cardiometabolic risk factor levels in 500 African American and white women in midlife. A VAT x SAT interaction term was evaluated. Results: The mean (±SD) age of the sample was 51.0 ± 2.9 y, and 37% were African American. Higher amounts of SAT and VAT were associated with higher cIMT, blood pressure, homeostasis model assessment insulin resistance index (HOMA-IR), and concentrations of glucose, triglycerides, and insulin and with lower concentrations of HDL cholesterol. However, in African Americans, but not in whites, higher amounts of VAT significantly attenuated associations between higher amounts of SAT and higher insulin concentrations (P for interaction = 0.032) and HOMA-IR (P for interaction = 0.011) and reversed associations with cIMT (P for interaction = 0.005) and glucose (P for interaction = 0.044). Conclusions: These results suggest that in midlife African American but not white women, adverse associations between abdominal SAT and cardiometabolic risk factors are attenuated and, in the case of subclinical atherosclerosis, are reversed as VAT amounts increase. Given that African American women suffer disproportionately from obesity and cardiovascular disease, further research into the role of this effect modification on obesity-associated vascular disease in African American women is warranted.