Introduction: Little is known about hemodynamic disturbances affecting cerebral hemispheres in traumatic brain injury (TBI) after cranioplasty. Methods: We prospectively investigated six stable TBI patients who underwent cranioplasty more than 90 days after effective decompressive craniectomy. Computerized tomography perfusion (CTP) studies and evaluation of clinical outcome were performed for each patient before cranioplasty and at 7 days and 3 months after surgery. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in multiple cortical circular regions positioned in cranioplasty-treated and contralateral hemispheres. Results: Neither complications associated with cranioplasty nor changes in outcome were observed. On the treated side, CBF and CBV values were higher before and 7 days after cranioplasty than at 3 months after surgery, whereas MTT values were lower at 7 days than at 3 months after surgical treatment. Conclusions: Our results indicate that cortical perfusion progressively declines in the cranioplasty treated hemisphere but remains stable in the contralateral hemisphere after surgery and suggest that CTP can represent a promising tool for a longitudinal analysis of hemodynamic abnormalities occurring in TBI patients after cranioplasty. In addition, these data imply a possible role of cranioplasty in restoring flow to meet the prevailing metabolic demand. © 2014 Springer-Verlag.