Background: Post-stroke depression (PSD) is a common consequence of stroke that negatively interferes with the rehabilitation outcome in patients. It remains unclear what relationship exists between the site and size of brain infarcts and the development of PSD and the risk factors for PSD. We conducted a MRI-based cohort study to examine the radiological correlations for PSD in Chinese patients with ischemic stroke. Methods: Our study included 163 patients with acute ischemic stroke. The diagnosis of PSD was made with World Health Organization Composite International Diagnostic Interview (WHO-CIDI), which is based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) during a follow-up exam at 3-month post stroke. The demographic, clinical, and detailed radiological variables (e.g., lesion location, and degree of white matter lesions) were also examined. Results: The univariate analyses suggested that the frequency of multiple acute infarcts, the total number and volume of acute infarcts were higher in the PSD group than those in the non-PSD group. In particular, PSD patients showed higher rates of infarcts in cortical-subcortical area of the frontal and temporal lobe as well as in internal capsule (including genu, anterior and posterior limb). The multivariate analysis suggested that independent radiological risk factors for PSD may include the presence of multiple acute infarcts, the infarct affecting either side of posterior limb of internal capsule, genu of internal capsule, and cortical-subcortical areas in the temporal lobe. Conclusion: Our study on ischemic stroke patients suggested that certain neuroanatomical factors (i.e., lesions at posterior limb and genu of internal capsule and cortical-subcortical area of the temporal lobe, as well as the presence of multiple acute infarcts) may correlate with the PSD development. (C) 2011 Elsevier B.V. All rights reserved.