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Past vascular depression research assumes that later\u2010life depressive symptoms relate uniquely to high CVB and not to prior, recurrent depression. This study examines these divergent hypotheses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data include 5175 participants across 18\u00a0years from the Wisconsin Longitudinal Study (mean age at 1993 baseline was 53\u00a0years; follow\u2010ups in 2004 and 2011). Depressive symptomatology was measured using the Center for Epidemiological Studies Depression. CVB was operationalized as hypertension, high blood sugar, diabetes, and other heart problems. Hypotheses were examined via a cross\u2010lagged structural equation model and logistic regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Model fit was acceptable (root mean square error of approximation (RMSEA)\u00a0=\u00a00.047; comparative fit index\u00a0=\u00a00.963). Hypotheses 1 and 2 were supported. Depressive symptomatology at 2004 and 2011 follow\u2010ups was predicted by earlier depressive symptomatology and prior CVB. Hypothesis 3 was partially supported; depressive symptomatology in 2004 predicted subsequent CVB. Logistic regression results were that CVB predicted clinically significant depressive symptoms based on the Center for Epidemiological Studies Depression clinical cutoff.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cerebrovascular burden in midlife predicts depressive symptomatology in later\u2010life, even after accounting for prior depressive symptomatology, supporting a fundamental assumption of the vascular depression hypothesis. Midlife depressive symptomatology also predicted escalation of CVB in later\u2010life. Results suggest a process model of later\u2010life depressive symptom development that interrelates CVB and depressive symptoms throughout the life span and have clinical implications for the interruption of this process through the integration of primary care and behavioral health specialists. 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