Background: Atherosclerosis in stroke-related vascular beds is the major cause of stroke. Studies demonstrated that multivascular atherosclerosis is prevalent in stroke patients and those with multivascular plaques had higher risk of recurrent stroke. Objectives: This study investigated the relationship between homocysteine and multivascular atherosclerosis in stroke-related vascular beds using magnetic resonance imaging. Methods: Patients with recent ischemic cerebrovascular symptoms were enrolled and underwent three-dimensional magnetic resonance vessel wall imaging for intracranial arteries, extracranial carotid arteries and aortic arch. Traditional risk factors and homocysteine were measured. Presence of multivascular plaques defined as plaques in at least two stroke-related vascular beds on magnetic resonance imaging was determined. The relationship between homocysteine and characteristics of multivascular plaques was determined. Results: Of 49 enrolled patients (mean age: 56.3 ± 13.8 years; 35 males), 23 had multivascular plaques. Homocysteine (odds ratio, 1.17; 95% confidence interval, 1.02–1.34; p = 0.022) and age (odds ratio, 1.71; 95% confidence interval, 1.22–2.41; p = 0.002) were significantly associated with presence of multivascular plaques. The adjusted associations remained significant (both p < 0.05). In discriminating presence of multivascular plaques, the area-under-the-curve of age, homocysteine and combination of them was 0.79, 0.70 and 0.87 respectively. Conclusions: Homocysteine is independently associated with stroke-related multivascular plaques and combination of age and homocysteine has stronger predictive value. © 2019 Elsevier Ltd