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Purpose: For a large hemispheric infarction, the clinical decision for decompressive surgery is commonly made on the basis of both radiological data showing brain swelling with herniation and concomitant neurological deterioration. However, for early decompressive surgery before clinical deterioration, strict cutoff criteria with a high specificity are required on the basis of timely assessment of the infarct volume. Materials and methods: Sixty-one patients who presented with a hemispheric infarction were initially evaluated using diffusion-weighted images (DWIs) within 14 h and computed tomography (CT) scans 24 ± 4 h after stroke onset to assess the infarct volume and midline shift. In addition, brain atrophy was evaluated using the bicaudate ratio. Twenty-one patients developed a malignant course, while 40 patients experienced a non-malignant course. Results: According to a receiver-operating characteristic curve analysis for 50 patients with a bicaudate ratio <0.16, an initial infarct volume >160 ml in the DWI achieved a 97% specificity and 76% sensitivity, while an initial infarct volume >135 ml achieved an 86% specificity and 91% sensitivity. For the follow-up CT scans, an infarcted lesion volume >220 ml and midline shift >3.7 mm provided a 100% and 98% specificity, respectively. Conclusions: For the patients who presented with an acute hemispheric infarction and had a bicaudate ratio <0.16, an initial infarct volume >160 ml in a DWI within 14 h after stroke onset is highly predictive of a malignant course. In addition, an infarct volume >220 ml or midline shift >3.7 mm in the follow-up CT approximately 24 h after stroke onset facilitates early surgical decompression before clinical deterioration. [ABSTRACT FROM AUTHOR]