Numerous reports have described a variety of clinical syndromes resulting from posterior cerebral artery (PCA) infarction, whereas only a few pathoanatomical and retrospective clinical studies have investigated the underlying mechanisms. Therefore we attempted to determine the causes of infarction in the superficial posterior cerebral artery (PCA) territory by means of a more comprehensive, modern vascular and cardiac study. During a 4-year period 74 consecutive patients (49 men, 25 women) with acute PCA infarction documented on CT (n = 74) and MRI (n = 41) were included in the study. Patients had a neurological examination, vascular studies [extra- and transcranial Doppler (n = 74), magnetic resonance (n = 31) or intra-arterial (n = 22) angiography], cardiac evaluation [ECG (n = 74), transthoracic (n = 74) and transoesophageal echocardiography (n = 30)], and coagulation tests. A cardiac source of embolism was established in 31%, significant vertebrobasilar artery disease in 22%, and PCA stenosis or occlusion in 8% of the patients. Rare causes, such as hypercoagulopathy or paradoxical embolism via a patent foramen ovale, were present in 15%. However, in spite of the comprehensive diagnostic evaluation, the cause of the stroke remained undetermined in 24% of the cases. Apart from complete infarcts of the posterior branches of the PCA, which occurred more frequently in cardioembolic strokes (18%, P < 0.05), the topographical patterns of infarct extension and the coincidence of infarction in the deep territories of the PCA, the cerebellum and brainstem were not significantly different among the causal subgroups. The frequency of haemorrhagic transformation (18%) was highest among cardioembolic strokes (44%, P < 0.001). This prospective study of PCA infarction demonstrated embolism from cardiac and vascular sources as the predominant cause. In contrast to previous studies, we found no evidence of migraine as a cause of PCA infarction, whereas paradoxical embolism was the presumed cause in a considerable number of cases. Whereas the cause of stroke could not reliably be derived from infarct topography, haemorrhagic transformation indicated there had been cardioembolism in most cases.