Vascular risk factors (VRFs) have been associated with stroke and cognitive impairment, however, the role of VRFs in predicting post-stroke depression (PSD) has not been assessed. The objective of the current study was to determine whether VRFs are associated with the risk of PSD in an acute stroke population. In this observational study, patients meeting World Health Organization MONICA Project and National Institute of Neurological Disorders and Stroke criteria for stroke were eligible. Patients were assessed for depression, cognition, and stroke severity, and VRF and demographic information were obtained. A total of 102 patients were recruited within 4 months post-stroke. Using a score of ≥16 on the Center for Epidemiological Studies Depression scale to determine depressive symptoms, 38 patients (age 72.1 ± 15.6, 44.7% male) screened positive for depressive symptoms and 64 (age 70.1 ± 13.6, 51.6% male) screened negative. Analysis of VRFs showed that only hypertension (P = .044) independently predicted the presence of depressive symptoms (χ² = 4.742, P = .029, Nagelkerke R² = .062). Hypertension was associated with post-stroke depressive symptoms, while there was no relationship between PSD and other VRFs. Hypertension may have a greater impact than other VRFs on mood following stroke and may have a role in prevention and treatment of PSD.