BACKGROUND: Vascular depression has been proposed as a unique diagnostic subtype in late life, yet no study has evaluated whether the specified clinical features associated with the illness are jointly indicative of an underlying diagnostic class. METHODS: We applied latent class analysis to two independent clinical samples: the prospective, cohort design, Neurocognitive Outcomes of Depression in the Elderly (NCODE) study and the 8-week, multicenter, double blind, placebo-controlled Old-Old study. RESULTS: A two-class model consisting of vascular and nonvascular depressed patients provided an excellent fit to the data in both studies, chi(2)(6) = 2.02, p = .90 in the NCODE study and chi(2)(6) = 7.024, p = .32 in the Old-Old study. Although all of the proposed features of vascular depression were useful in identifying the illness, deep white matter lesion burden emerged with perfect sensitivity (1.00) and near-perfect specificity (.95), making it the only indicator necessary to determine class membership. CONCLUSIONS: These findings, replicated across two independent clinical samples, provide the first support for the internal validity of vascular depression as a subtype of late-life depression.