During the first hours after acute ischemic stroke, the CT usually shows no abnormalities. Therapeutic trials of ischemia in the middle cerebral artery (MCA) territory involves decision-making when the CT may not show obvious ischemic changes. We reviewed 100 consecutive patients, admitted within 14 hours after a first stroke. Selective criteria were clinical presentation with MCA ischemia and at least two CTs (1 initial and 1 control). All CTs were retrospectively analyzed by at least two physicians blinded to the patient's status. On the first CT, early signs were hyperdense MCA sign (HMCAS), early parenchymatous signs (attenuation of the lentiform nucleus [ALN], loss of the insular ribbon [LIR], and hemispheric sulcus effacement [HSE]), midline shift, and early infarction. Subsequent infarct locations were classified according to total, partial superficial (superior or inferior), deep, or multiple MCA territories. Clinical features, etiology, and Rankin scale were collected. There were 52 women (mean age 70.8). The CTs were performed at mean 6.4 hours (1 to 14 hours) and before the sixth hour in 62% of the patients. Early CT was abnormal in 94% of the cases, and the abnormalities found were an HMCAS in 22 patients, ALN in 48, LIR in 59, HSE in 69, midline shift in 5, and early infarct in 7. CT was normal in six patients where it was performed earliest (mean 4.5 hours) and in the oldest patients (mean age 80.1). Early parenchymatous CT signs were significantly associated with subsequent MCA infarct location and extension: ALN and deep infarct, HSE and superficial infarct, LIR and large infarct. HMCAS was never found in isolation and was always associated with the three other signs in extended MCA infarct. The presence of two or three signs (ALN, LIR, or HSE) was associated with extended MCA infarct (p < 0.001) and poor outcome (p < 0.001). Our findings suggest that CT frequently discloses parenchymal abnormalities during the first hours of ischemic stroke. Early signs allow the prediction of subsequent infarct locations; CT may provide a simple tool in evaluating the early prognosis of MCA infarction and thus may be useful in selecting better treatments.