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Objectives: To investigate whether vascular care slows dementia progression in patients with Alzheimer’s disease with cerebrovascular lesions on neuroimaging.; Design: Multicenter randomized controlled clinical trial with 2-year follow-up.; Setting: Neurological and geriatric outpatient clinics in 10 Dutch hospitals: three academic, five teaching, and two midsize community hospitals.; Participants: One hundred thirty community-dwelling patients with mild dementia fulfilling clinical criteria for Alzheimer’s disease with cerebrovascular lesions on neuroimaging.; Intervention: Patients randomized to vascular care were treated according to strict guidelines for hypercholesterolemia and hypertension. Acetylsalicylic acid, folic acid, and pyridoxine were prescribed. During visits every 3 months special attention was paid to smoking cessation, losing weight, and stimulating physical exercise.; Measurements: Primary outcome was disability, measured according to the Interview for Deterioration in Daily activities in Dementia (IDDD). Secondary outcomes were changes on the Mini-Mental State Examination (MMSE), the Revised Memory and Behavioural Problems Checklist (RMBPC), a composite measure of “poor outcome” (death, institutionalization, or severe clinical decline), and costs.; Results: Patients in the vascular and standard care condition declined equally on the IDDD (13.7 vs 11.0 points; difference 2.7, 95% confidence interval = -3.1-8.6). There was no treatment effect on the MMSE or RMBPC. There were no differences in institutionalization rate, “poor outcome” (41.4% vs 35.4%, P=.50), or costs. In the intervention group, there were three intracerebral hemorrhages and one gastrointestinal hemorrhage, versus none in the control group.; Conclusion: Multicomponent vascular care, combining pharmacological and nonpharmacological interventions, does not slow decline in patients with Alzheimer’s disease with cerebrovascular lesions.;