Objective To analyze the postoperative complications and prognosis of the patients undergoing cranioplasty at different stages after decompressive craniectomy, and to explore the optimal timing of cranioplasty after decompressive craniectomy for skull defect. Methods We retrospectively analyzed the clinical data of 83 patients who underwent cranioplasty from Nov. 2012 to Nov. 2015. According to the different timing of cranioplasty after decompressive craniectomy, the patients were divided into the early-stage group (≤3 months, n=31) and the late-stage group (>3 months, n=52). We recorded and compared the incidence of postoperative complications in the two groups. The Glasgow outcome score (GOS) and Karnofsky performance status (KPS) score were used to evaluate the prognosis of the patients in the two groups. Results The incidence of hydrocephalus in the early-stage group (16.13%, 5/31) was significantly higher than that in the late-stage group (1.92%, 1/52; P<0.05), while the incidence of other postoperative complications was not significantly different. And the GOS score and KPS score of the early-stage group were significantly higher than those of the late-stage group (GOS score: 4.16±0.86 vs 3.63±0.72, P<0.05; KPS score: 80.32±16.22 vs 70.19±16.27, P<0.05). Conclusion Early cranioplasty after decompressive craniectomy can improve the neurological function and prognosis of the patients with traumatic brain injury, but it may increase the incidence of hydrocephalus.