Background: Diffusion-weighted image (DWI) might be useful to predict the prognosis of acute hypoxic encephalopathy. The aim of our study was to test whether the early change and extent of DWI abnormalities can be an indicator of the clinical outcome of hypoxic encephalopathy. Methods: Forty-four patients who were diagnosed as hypoxic encephalopathy due to the cardiorespiratory arrest were retrospectively identified. Clinical variables were determined, and the DWI abnormalities were counted by four areas: cortex, subcortical white matter, cerebellum and deep grey matter, and were divided into three groups by the extent of lesions. Prognosis was classified as 'poor' (Glasgow coma scale (GSC) at 30 days after arrest <9 or death) and 'good' (GSC at 30 days after arrest ≥9). Results: GCS at day 3 (p<0.001), presence of seizure (p=0.01), and presence of lesion (p<0.001) were significantly different in prognosis, but statistically there is no association with the extent of lesions and prognosis (p=0.26). Conclusions: Presence of early DWI changes could predict the clinical outcome of hypoxic encephalopathy after cardiorespiratory arrest.