It is unclear how soon after a decompressive hemicraniectomy that cranioplasty be safely performed in a patient in whom the ICP has been normalized. Early surgery has been associated with infection, intracerebral hematoma, and complications due to persistent or recurrent brain edema. Delayed cranioplasty of large cranial defects exposes the patient to different conditions known in the literature as the syndrome of the sinking skin flap. The purpose of this study was to investigate the hypothesis that timing of cranioplasty after decompressive hemicraniectomy influences outcome and complications. We retrospectively examined outcome after cranioplasty performed at < 7 weeks, 7-12 weeks, and > 13 weeks after craniectomy in patients with large cranial defects after decompressive hemicraniectomy in our institution between 1997 and 2008. The time between craniectomy and cranioplasty ranged from 17 days to 4 months depending on several factors such as: the cause of decompression, infection before or after craniectomy, and skin flap concavity. The analysis of the registered postoperative complications revealed that there were no significant differences between the examined groups. The cranioplasty at < 7 weeks, in the form of reimplantation of the own skull flap, led to a GOS improvement of 78 %, at 7-12 weeks 46 % and at > 13 weeks12 %, respectively. Pairwise comparisons showed that the difference between cranioplasty at < 7 weeks versus 7-12 weeks or > 13 weeks cranioplasty groups was statistically significant ( = 0.05 and < 0.001, respectively). Our study suggests that many patients with large cranial defects after decompressive craniectomy can safely undergo cranioplasty in an early stage; direct answers to these questions of timing of cranioplasty are best addressed by prospective studies. Nevertheless, the present study provides a basis for decision-making in certain patients and for the design of future investigations.