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Objectives Small subcortical infarcts ( SSI) frequently coexist with brain white matter hyperintensity ( WMH) lesions. We sought to determine whether preexisting WMH burden relates to SSI volume, SSI etiology, and 90-day functional outcome. Materials and methods We retrospectively studied 80 consecutive patients with acute SSI. Infarct volume was determined on diffusion weighted imaging, and WMH burden was graded on fluid-attenuated inversion recovery sequences according to the Fazekas scale. SSI etiology was categorized as small vessel disease ( SVD) vs non- SVD related. Multivariable linear and logistic regression models were constructed to determine whether WMH burden was independently associated with the SSI volume and a poor 90-day outcome (modified Rankin scale [ mRS] score >2), respectively. Results In unadjusted analyses, patients with non- SVD-related SSI were older ( P=.002) and more frequently had multiple infarcts ( P<.001) than patients with SVD-related SSI. In the fully adjusted model, WMH severity (Coefficient 0.07; 95%- CI 0.029-0.117; P=.002) but not SSI etiology ( P>.1) was independently associated with the SSI volume. On multivariable logistic regression, worse WMH ( OR 2.28; 95%- CI 1.04-4.99; P=.040), SSI etiology ( OR 9.20; 95%- CI 1.04-81.39; P=.046), preadmission mRS ( OR 8.96; 95%- CI 2.65-30.27; P<.001), and SSI volume ( OR 1.98; 95%- CI 1.14-3.44; P=.016) were associated with a poor 90-day outcome. Conclusions Greater WMH burden is independently associated with a larger SSI volume and a worse 90-day outcome. [ABSTRACT FROM AUTHOR]