OBJECTIVES: To examine the association between cerebral hyperintensities and cerebrovascular risk factors (CVRF) among middle-aged and older adults with major depressive disorder (MDD). METHODS: Thirty patients (aged 55-77 years) with MDD and no history of stroke participated in a magnetic resonance imaging assessment to assess for the presence of cerebral hyperintensities and underwent a physical examination to assess stroke risk as indexed by the Framingham Stroke Risk Profile (FSRP). In addition, intima medial thickness (IMT) was measured in the left and right carotid arteries. RESULTS: Higher FSRP levels were associated with total greater cerebral hyperintensities (r = 0.64), as well as greater subependymal hyperintensities (r = 0.47), confluent periventricular changes (r = 0.46), and tended to be associated with subcortical gray matter hyperintensities (r = 0.34). A quadratic relationship was observed between IMT and total cerebral hyperintensities (b = 4.84), and higher IMT levels were associated with greater subependymal hyperintensities (r = 0.40). CONCLUSIONS: Higher levels of CVRF are associated with graded increases in cerebral hyperintensities among middle-aged and older adults with MDD.