Despite growing information, questions still surround various aspects of post-stroke depression (PSD). The Italian multicenter observational study Destro was designed to help clarify in a large sample the frequency and clinical impact of PSD. A total of 53 centers consecutively admitted 1064 patients with ischemic or hemorrhagic stroke, assessing them periodically in the first 9 months after the event. Patients with depression were followed for two years. Depression was diagnosed on clinical examination, verbal (Beck Depression Inventory) and non-verbal rating systems (Visual Analog Mood Scale), identifying the nosographic condition attributable to the mental state. The patient's clinical history, residual independence, and post-ictus quality of life were also taken into account. PSD was detected in 383 patients (36 %), most of whom had minor depression (80.17 %), with dysthymia, rather than major depression and adaptation disorder. About 80% developed depression within three months of the stroke. Cases with later onset tended to have less severe symptoms. Risk factors were a history of depression, severe disability, previous stroke and female sex, but not the type and site of the vascular lesion. PSD was not correlated with any increase in mortality or cerebrovascular recurrences, but these patients had lower autonomy and quality of life ratings. In conclusion, patients should be close observed in the first few weeks after a stroke in order to check for depression,which is more likely in those with clear risk factors and may spoil their quality of life.