: We assessed if γ' fibrinogen, an isoform of fibrinogen, is independently associated with subclinical atherosclerosis beyond total fibrinogen in black and white men and women participating in the Atherosclerosis Risk in Communities study. Fasting γ' fibrinogen was measured in 6847 Atherosclerosis Risk in Communities participants, ages 51-70 years, in 1993-1995. Carotid intima-media far wall thickness (CIMT) was measured by B-mode ultrasonography at the common, internal and bifurcation carotids. The association of γ' fibrinogen tertiles with overall and segment-specific mean CIMT was assessed with linear regression, controlling for fibrinogen as well as cardiovascular risk factors, including high-sensitivity C-reactive protein and D-dimer. γ' Fibrinogen values ranged from 8.0 to 80.3 mg/dl and were positively related to age, female sex, black race, smoking, BMI, lipids and SBP. Crude γ' fibrinogen was directly associated with all CIMT measures except for the internal carotid, but explained less than 1% of the variance in the associations. Adjustment for total fibrinogen eliminated these associations, and total fibrinogen remained an independent predictor of CIMT without explaining additional variance. Adjustment for potential confounding variables did not alter the observed associations, which did not differ by race or sex. In these cross-sectional data, γ' fibrinogen was not independently associated with CIMT when controlling for total fibrinogen. γ' Fibrinogen and total fibrinogen together explained a very small proportion of the variance in CIMT, regardless of the carotid site. If γ' fibrinogen adds to total fibrinogen's ability to predict subclinical atherosclerosis, it may be in younger populations.