Trans-fatty acids (TFA) increase cardiovascular disease risk and have been associated with the cardiovascular risk factors body mass index (BMI) and waist circumference (waist) in persons without diabetes. Whether TFA are associated with BMI and waist in persons with type 2 diabetes is unknown. We investigated the association between TFA exposure as indicated by plasma concentrations of 18-carbon TFA and BMI and waist. We studied persons randomized into Look AHEAD at two clinics (Baltimore, n=81; Houston, n=151) who participated in a substudy assessing physical activity and an ancillary study of oxidative stress and completed the Look AHEAD Food Frequency Questionnaire (LAFFQ). Look AHEAD is a multi-center controlled trial of lifestyle intervention for weight loss in overweight or obese adults (aged 45-76) with type 2 diabetes. Representation of women (57%) and minorities (18.1% black, 8.2% Hispanic, 3.9 % other race/ethnicity) was similar to Look AHEAD. Before intervention, weight, height, and waist were measured, BMI was calculated, nutrients were estimated from LAFFQ, and physical activity was determined by accelerometry. TFA, saturated (SFA) and cis-monounsaturated (c-MFA) fatty acids were measured before intervention in plasma collected between December 2002 and April 2004. TFA intake in subjects was high (median 2.4% of energy, interquartile range 1.9%, 3.0%). In models adjusted for age, sex, race/ethnicity, clinic, sampling time, physical activity, and plasma total fatty acid concentration, BMI (p=0.0004) and waist (p=0.0018) varied according to plasma TFA concentration. For lowest, middle, and highest tertiles of plasma TFA, BMI was (mean+SE) 33.0+0.9, 36.9+0.9, and 36.6+0.9 kg/m 2 , respectively, while waist was 108.4+1.9, 115.8+1.9, and 114.8+2.0 cm, respectively. These associations were not attenuated by sequential adjustment for plasma SFA and c-MFA concentrations and for dietary variables including TFA, total fat, SFA, oleic acid, protein and total calories. These results extend findings concerning TFA exposure and BMI and waist circumference to persons with type 2 diabetes and are consistent with the notion that reducing TFA exposure may reduce cardiovascular risk in persons with type 2 diabetes.