BACKGROUND: Presence of femoral atheromatic plaques, an emerging cardiovascular disease (CVD) biomarker additional to carotid plaques, is poorly investigated in conditions associating with accelerated atherosclerosis such as Rheumatoid Arthritis (RA), Human Immunodeficiency Virus (HIV) infection and Type 2 Diabetes Mellitus (T2DM). OBJECTIVE/METHODS: To assess the frequency of femoral/carotid subclinical atheromatosis phenotypes in RA, HIV and T2DM and search for each disease-specific probability of either femoral and/or carotid subclinical atheromatosis, we examined by ultrasound a single-center cohort of CVD-free individuals comprised of consecutive non-diabetic patients with RA (n=226) and HIV (n=133), T2DM patients (n=109) and non-diabetic individuals with suspected/known hypertension (n=494) who served as reference group. RESULTS: Subclinical atheromatosis--defined as local plaque presence in at least on arterial bed--was diagnosed in 50% of the overall population. Among them, femoral plaques only were found in 25% of either RA or HIV patients, as well as in 16% of T2DM patients and 35% of reference subjects. After adjusting for all classical CVD risk factors, RA and HIV patients had comparable probability to reference group of having femoral plaques, but higher probability (1.75; 1.17-2.63 (odds ratio; 95% confidence intervals), 2.04; 1.14-3.64, respectively) of having carotid plaques, whereas T2DM patients had higher probability to have femoral and carotid plaques, albeit, due to their pronounced dyslipidemic profile. CONCLUSION: RA and HIV accelerate predominantly carotid than femoral. A "two windows" carotid/femoral, rather than carotid alone ultrasound, screening improves substantially subclinical atheromatosis detection in patients at high CVD risk.