Purpose: To determine the incidence and risk factors of postoperative infection after cranioplasty in patients with traumatic brain injury (TBI). Methods: Data of 289 adult patients who underwent cranioplasty after TBI at a single regional trauma center between year 2018 and 2021 were reviewed retrospectively. Patient characteristics and various procedural variables, such as interval between craniectomy and cranioplasty, estimated blood loss, laterality and materials of the bone flap, and duration and classification of perioperative antibiotics usage were analyzed. Results: Postoperative infection occurred in 17 patients (5.9%). Onset time of infectious symptom ranged from 9 days to 174 days (median, 24 days) after cranioplasty. The most common cultured organism was Staphylococcus aureus (47.1%), followed by Klebsiella pneumoniae (17.6%) and Enterococcus faecalis (17.6%). Patients with postoperative infection were more likely to have diabetes (odds ratio [OR], 6.96; 95% confidence interval [CI], 1.92–25.21; P=0.003), lower body mass index (OR, 0.81; 95% CI, 0.66–0.98; P=0.029), and shorter duration of perioperative antibiotics (OR, 0.83; 95% CI, 0.71–0.98; P=0.026). Conclusions: For TBI patients with diabetes, poor nutritional status should be managed cautiously for increased risk of infection after cranioplasty. Further studies and discussions are needed to determine an appropriate antibiotics protocol in cranioplasty.