Introduction: Late-life depression is a well-known risk factor for future dementia. Increasing evidences also show a link between cerebral hypoperfusion and neurodegeneration, although data on Transcranial Doppler ultrasonography (TCD)-derived measures in patients with "Vascular Depression" (VD) are lacking. The aim of this study was to assess and correlate TCD parameters with cognitive function and severity of subcortical ischemic vascular disease in a sample of VD patients. Methods: Seventy six patients (mean age 72.5 ± 5.3 years; 53.9% females) met the DSM-5 diagnostic criteria for unipolar major depression. Mean blood flow velocity (MBFv) and pulsatility index (PI) were recorded from the middle cerebral artery. Quantification of depressive symptoms (17-item Hamilton Depression Rating Scale -HDRS), neuropsychological test evaluating frontal lobe abilities (Stroop Color-Word test interference-Stroop T), and white matter lesions (WMLs) load according to the Fazekas visual score were also assessed. Results: WMLs severity was mild in 20 patients (group I), moderate in 32 (group II), and severe in 24 (group III). The groups were comparable in terms of clinical features, vascular risk factors profile, and HDRS score, whereas Stroop T score was worse in group III. An increased PI and a reduced MBFv were found in VD patients with severe WMLs. According to the regression analysis, a reduced MBFv was independently and significantly associated with depressive symptoms and executive dysfunction, even after adjusting for demographic features and vascular risk factors. Similarly, an independent and significant association was observed between the increase of PI and both Stroop T and WMLs severity. Conclusions: A TCD profile of low perfusion and high vascular resistance in VD patients suggests a diffuse cerebrovascular pathology likely arising from the small vessels and then extending to larger arteries. Hemodynamic dysfunction might play a pathogenic role in the development of cognitive impairment in patients with late-life depression and subcortical ischemic vascular disease. TCD represents a valuable tool in the early detection, assessment, and management of VD patients at risk for dementia.