Cranioplasties are performed to protect the brain and correct cosmetic defects, but there is growing evidence that this procedure may result in neurological improvement. We prospectively studied cranioplasties performed at our hospital over a 5-year period. The National Institute of Health Stroke Scale and Barthel index were recorded prior to and within 72 h after the cranioplasty. A perfusion computed tomography (PCT) and transcranial Doppler sonography (TCDS) were performed prior to and 72 h after the surgery. For the PCT, regions irrigated by the anterior cerebral artery, the middle cerebral artery (MCA), the posterior cerebral artery, and the basal ganglia were selected, as well as the mean values for the hemisphere. The sonography was performed in the sitting and the supine position for the MCA and internal carotid. The velocities, pulsatility index, resistance index, and Lindegaard ratio (LR) were obtained, as well as a variation value for the LR (DLR = LR sitting -LR supine). Fifty-four patients were included in the study. Of these, 23 (42.6%) patients presented with objective improvement. The mean cerebral blood flow of the defective side (m-CBF-d) increased from 101.86 to 117.17 mL/100 g/min ( p = 0.064), and the m-CBF of the healthy side (m-CBF-h) increased from 128.14 to 145.73 mL/100 g/min ( p = 0.028). With regard to the TCDS, the DLR was greater on the defective side prior the surgery in those patients who showed improvement (1.295 vs. -0.714; p = 0.002). Cranioplasty resulted in clinical improvement in 40% of the patients, with an increase in the post-surgical CBF. The larger variations in the LR when the patient is moved from the sitting to the supine position might predict the clinical improvement.