Objective: Embolism from a proximal source to the retinal circulation could be a sign of embolism from the same source to the hemispheric circulation. We sought to determine the frequency of acute brain infarcts on diffusion-weighted imaging (DWI) in patients with monocular visual loss of presumed ischemic origin (MVL). Methods: We retrospectively studied 129 consecutive patients with MVL secondary to retinal ischemia. All patients underwent DWI, comprehensive ophthalmologic and neurologic examination, and diagnostic evaluations for the underlying etiology. Statistical analyses explored univariate and multivariate predictors of DWI evidence of acute brain infarcts. Results: DWI revealed concurrent acute brain infarct(s) in 31 of the 129 patients (24%). The probability of positive DWI was higher in embolic versus nonembolic MVL (28 vs 8%, p = 0.04), in MVL characterized by permanent visual loss versus transient symptoms (33 vs 18%, p = 0.04), and in MVL associated with concurrent hemispheric symptoms versus isolated MVL (53 vs 20%, p < 0.01). Patients with positive DWI were more likely to harbor a major underlying etiology as compared to those with normal DWI (odds ratio, 3.7; 95% confidence interval, 1.59.4). Interpretation: This study demonstrates that MVL does not always represent an isolated disease of the retina; approximately 1 of every 4 patients with MVL demonstrates acute brain infarcts on DWI. Because patients with concurrent brain infarcts are more likely to exhibit a cardiac or vascular source of embolism, imaging evidence of brain injury in patients with MVL may be a useful marker to guide the timing and extent of diagnostic examinations. ANN NEUROL 2012;72:286293.