The aim of this study was to evaluate the applicability, sensitivity, and predictive power of diffusion-weighted MR imaging (DWI) in the diagnosis of vertebrobasilar infarction. From 1997 to 2002, we prospectively recruited 268 patients with acute signs and symptoms suspective of vertebrobasilar ischemia. The patients underwent biplanar EPI-T2 and EPI DWI within 24 h after onset of symptoms and high-resolution MRI as a control within 7 days. One hundred twenty-one patients had additional CT scanning. The DWI revealed acute vertebrobasilar infarction in 71.0%. The mean time exposure of DWI was 8 min and thus no more than that of CT imaging. It showed significantly more acute lesions than CT imaging (28.0%), but additional high-resolution MRI was not able to reveal more lesions than DWI alone. Even in 42 patients with reversible brainstem or cerebellar symptoms classified as TIA or PRIND, DWI demonstrated acute ischemia in 42.8%. Sixty-three patients with optimal final diagnosis of vertebrobasilar ischemia had normal DWI. One week after onset of symptoms, 88.9% of these patients had recovered completely or showed minimal symptoms. Therefore, DWI is a sensitive indicator of acute vertebrobasilar ischemia. It is no more time-consuming than CT imaging, and normal DWI is a predictor of good clinical outcome in patients with brainstem or cerebellar infarction.