The indications for cranioplasty after decompressive craniectomy are cosmetic repair and, mainly, restoration of cerebral protection. Although neurological improvement after cranioplasty is repeatedly noted, the reasons for this remain unclear. Few observations concerning the impact of cerebrospinal fluid hydrodynamic and/or atmospheric pressure have been published during the last decades. Relevant data concerning the cerebrovascular reserve (CVR) capacity and cerebral glucose metabolism before and after cranioplasty have been lacking until now. To gain further insight, this study was undertaken to investigate the impact of cranioplasty on indices of cerebral blood flow regulation and metabolism. Thirteen patients in whom extensive craniectomies had been performed underwent a meticulous study of blood flow velocities in the middle cerebral artery (MCA) and extracranial internal carotid artery (ICA), as assessed by transcranial Doppler ultrasonography during postural maneuvers (supine and sitting positions) and during stimulation with 1 g of acetazolamide for the interpretation of CVR capacity. Twelve patients underwent 18-fluorodeoxyglucose positron emission tomography. These measurements were obtained before and 7 days after cranioplasty. Cranioplasty improved preoperative differences in MCA blood flow velocities when comparing those in the injured with those in the uninjured hemisphere. Similarly, cranioplasty resolved decreases in extracranial ICA blood flow in the injured hemisphere that were induced by postural changes, which was a constant finding prior to this procedure. More strikingly, however, the CVR capacity, which was severely impaired in both hemispheres, increased significantly after the procedure. Metabolic deficits, which were observed in the injured hemisphere, were found to improve after reimplantation of the skull bone flap. Cranioplasty appears to affect postural blood flow regulation, CVR capacity, and cerebral glucose metabolism markedly. Thus, early cranioplasty is warranted to facilitate rehabilitation in patients after decompressive craniectomy.