BACKGROUND: White matter lesions (WML) and lacunar infarcts (LI) are believed to have microvascular etiologies but the exact microvascular changes occurring in each is unclear. AIM: Using the retina as a proxy, we assessed retinal microvascular changes in WML and LI. METHODS: We prospectively recruited 1211 acute stroke patients. Four subgroups were identified from neuroimaging: WML alone, LI alone, both WML and LI, neither WML nor LI. Masked retinal photographs identified retinopathy and retinal arteriolar wall signs and measured retinal vascular caliber. RESULTS: Compared with 448 controls with neither WML nor LI, 384 patients with only WML were more likely to have retinopathy [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1 to 2.1] and enhanced arteriolar light reflex (OR 1.6, 95% CI 1.1 to 2.3); 200 patients with only LI were more likely to have arteriolar narrowing (OR 1.6, 95% CI 1.1 to 2.3) and enhanced arteriolar light reflex (OR 1.6, 95% CI 1.0 to 2.4); and 179 patients with both WML and LI were more likely to have arteriovenous nicking (OR 1.7, 95% CI 1.1 to 2.6), enhanced arteriolar light reflex (OR 2.0, 95% CI 1.3 to 3.2) and wider venules (OR 2.3, 95% CI 1.4 to 3.6). All analyses were adjusted for age, gender, study site and cardiovascular risk factors. CONCLUSION: Both WML and LI were associated with retinal microvascular signs, supporting a microvascular etiology. Differing patterns of association suggest different mechanisms may predominate, e.g. greater endothelial permeability in WML, and ischemia associated with arteriolar wall disease in LI.