Background and aims: Several epidemiological studies have shown that hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke in both men and women, presumably by accelerating vascular atherosclerosis. However, the contribution of gender for homocysteinedriven atherosclerosis is still matter of controversy. Methods: In this study we aimed to investigate the genderspecific effects of homocysteine serum levels on indicators of carotid atherosclerosis (i.e. intima–media thickness (IMT) and plaque characteristics) in apparently healthy individuals. For this, recruited individuals aged ≥18 years underwent comprehensive medical history collection, physical examination, blood sampling, and carotid DopplerDuplex ultrasound. Results: The study included 300 apparently healthy subjects with a mean age of 49.9±14.5 years, including 180 (60%) women and 120 (40%) men. High levels of homocysteine were observed in 166 (55%) subjects, with comparable women to men ratio. Seric homocysteine levels significantly correlated with IMT (r=0.18, p<0.001), number of carotid plaques (r=0.24, p<0.001), and total plaque area (r=0.25, p<0.001) in women but not in men. Subjects with elevated homocysteine displayed higher values of IMT (t=-2.6, p=0.008), higher number of carotid plaques (Z=-2.5, p=0.01), and higher total plaque area (Z=-2.5, p=0.008) compared to subjects with normal homocysteine levels. Seric levels of homocysteine yielded an AUC of 0.68 (95% CI 0.54-0.82) and 0.64 (95% CI 0.57-0.71) in discriminating women with normal/abnormal IMT and women with/ without plaques, respectively. Conclusion: Our findings suggest that only women show a specific association between seric homocysteine levels and carotid atherosclerosis, considered a subclinical marker of stroke risk. Disclosure: Nothing to disclose.