This study investigated subclinical atherosclerosis progression in low-risk, middle-aged adults (N=141; mean age 49.6±4.7 years) using a 5-year ultrasound follow-up. We compared in-volvement of the carotid and femoral arteries. Methods: Clinical data, risk factors, and carotid/femoral intima-media thickness (IMT) and plaque presence were analyzed. Results: Cardiovascular risk factors and scores increased significantly at follow-up. Both carotid and femoral IMT increased (p<0.001) but remained within the normal range. While plaque prev-alence rose and was similar in both arteries (carotid: 4.8% to 17.9%, femoral: 3.6% to 17.7%, p<0.001 for both), the progression of plaque burden was greater in femorals. Notably, carotid IMT demonstrated a faster yearly progression rate compared to femoral IMT. The age- and sex-adjusted increase in IMT was also more frequent in the carotids (52.9% to 78.8%, p<0.001) compared to femorals (23.2% to 44.7%, p<0.001). Conclusions: This study demonstrates significant subclinical atherosclerosis progression in low-risk middle-aged adults during 5 years. Carotid arteries showed a faster progression rate and higher prevalence of increased age- and sex-adjusted IMT compared to the femoral arteries. However, plaque burden was similar in both territories, with greater progression in femorals. Identifying carotid and femoral atherosclerosis burden may be a valuable tool for risk stratification in this population.