Objective: The vascular depression hypothesis posits that depression can arise in late life from cerebrovascular damage and that depression arising this way has a different clinical presentation and is more chronic and treatment-resistant than early-onset depression, This study tested the relationship of cerebrovascular risk factors (CVRF) to clinical presentation and treatment outcome in 156 subjects enrolled in a long-term maintenance treatment study of late-life recurrent major depression. Methods: CVRF scores were generated with the Probability of Stroke Risk Profile. Subjects with the highest one-third of scores were designated High CVRF, and their baseline clinical presentation and treatment outcomes were compared with the remaining subjects, Results: In the High-CVRF group, a greater proportion of subjects had first-onset depression after age 60. However, high CVRF score, late onset of depression, and their interaction had no effect on time-to-remission, need for adjunctive medication, or increased risk for recurrence during 3-year follow-up. Furthermore, high CVRF score and late onset of depression did notpredict the associated clinical features of vascular depression, such as psychomotor retardation and lack of insight, previously described in the literature. Conclusion: Optimism about the outcome of late-life depression treatment should not be diminished by the presence of high cerebrovascular risk.