Object: Patients surviving initial decompressive craniectomy are needed to undergo cranioplasty, which is potentially complicated by postoperative seizures. The definite incidence of post-cranioplasty seizures and application of prophylactic antiepileptic drugs remain controversial. Methods: We performed systematic review to clarify these issues. Searching through PubMed, Ovid, Web of Science and Cochrane library databases, we included publications recording the incidence of seizures after cranioplasty and prophylactic treatment. We pooled the respective incidence of seizures and 95% confidence interval (CI). The overall effect was expressed with events per 1,000 person-years calculated by the mean follow-up time. Trim and fill method was used to adjust for publication bias. Subgroup analyses were conducted to examine the differences in incidences of seizures. Results: Two randomized and 14 observational studies were extracted. The pooled incidence of post-cranioplasty seizures was 0.092 (95%CI 0.063, 0.121), which decreased to 0.043 (95%CI 0.010, 0.076) after adjustment. The summarized incidences of early seizures and late seizures were 0.074 (95%CI 0.029, 0.119) and 0.053 (0.027, 0.079) respectively. In the subgroup analyses, randomized studies reported a higher incidence than observational studies, and early cranioplasty (<6 months) resulted in an increased incidence compared with late cranioplasty (>6 months). The overall effect from two randomized studies showed prophylactic antiepileptic drugs reduced nearly 80% of seizures. Conclusion: The estimated incidence of post-cranioplasty seizures is 43 per 1,000 person-years after adjustment. The incidence of early seizures is obviously higher than that of late seizures. Moreover, early cranioplasty leads to more post-cranioplasty seizures than late cranioplasty does. Based on the present evidences, the application of prophylactic antiepileptic drugs effectively reduces seizures.