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Aesthetic appearance and brain protection are the main indications for cranial reconstruction following decompressive craniectomy. Recently, few reports indicated that cranioplasty could also improve both, cognitive and functional status. A group of 20 patients were treated with decompressive craniectomy following closed head injury; among these patients, two of them (who represent the subject of the current investigation) had to undergo subsequent cranioplasty removal due to the development of local infection. All patients were evaluated by Glasgow outcome scale, frontal assessment battery and mini-mental state examination at 1 week before completion of the cranioplasty as well as 6 and 24 weeks following cranioplasty. Perfusion computed tomography scans were also performed (1 week before and 6 weeks after cranioplasty) as well as a trans-cranial Doppler 1 week before, and 6 and 24 weeks after. The two patients being the subject of this study were also clinically and radiologically evaluated after cranioplasty removal. These two patients, who represent (not intentionally) two case control, showed a real clinical and cerebral perfusion improvement following repair of the skull defect followed by obvious clinical worsening after the skull flap had to be removed. Cranioplasty is likely not to have just a positive influence on cosmetic and protective features of the patients but also seem to improve both, cognitive and functional status by favorably influencing local and global brain hemodynamic and perfusion.