Objectives: Depression is the most common affective disorder following stroke yet the neuroanatomical model of poststroke depression (PSD) remains unclear. This study examined the association between PSD and cerebral microbleeds (CMBs) and hypothesized that CMBs in specific regions would be associated with PSD. Methods: Of the 4766 patients with first ever or recurrent acute ischemic stroke admitted to the Acute Stroke Unit of the Prince of Wales Hospital between June 2004 and October 2010, 229 met the entry criteria and formed the study sample. Patients with a Geriatric Depression Scale score of 7 or above were classified as having PSD. The presence and location of CMBs were evaluated with magnetic resonance imaging. Results: Compared to the non-PSD group, patients with PSD were more likely to have pontine CMBs (32.0% vs 18.2%; P = .019). The presence of pontine CMBs remained an independent predictor of PSD in the multivariate analysis, with an odds ratio of 2.2 ( P = .016). Conclusion: The results suggest that pontine CMBs are associated with a higher risk of developing PSD.