BACKGROUND: There is no consensus on which material is best suited for repair of cranial defects. OBJECTIVE: To investigate the outcomes following custom-made titanium cranioplasty. METHODS: The medical records for all patients who had titanium cranioplasty at 2 major neurosurgical centers in Western Australia were retrieved and analyzed for this retrospective cohort study. RESULTS: Altogether, 127 custom-made titanium cranioplasties on 113 patients were included. Two patients had 3 titanium cranioplasties and 10 patients had 2. Infected bone flap (n = 61, 54%), either from previous craniotomy or autologous cranioplasty, and contaminated bone flap (n = 16, 14%) from the initial injury were the main reasons for requiring titanium cranioplasty. Complications attributed to titanium cranioplasty were common (n = 33, 29%), with infection being the most frequent complication (n = 18 patients, 16%). Complications were, on average, associated with an extra 7 days of hospital stay (interquartile range 2-17). The use of titanium as the material for the initial cranioplasty (P = .58), the presence of skull fracture(s) (P . .99) or scalp laceration (s) (P = .32) at the original surgery, and proven local infection before titanium cranioplasty (P = .78) were not significantly associated with an increased risk of infection. Infection was significantly more common after titanium cranioplasty for large defects (hemicraniectomy [39%] and bifrontal craniectomy [28%]) than after cranioplasty for small defects (P = .04). CONCLUSION: Complications after using titanium plate for primary or secondary cranioplasty were common (29%) and associated with an increased length of hospital stay. Infection was a major complication (16%), and this suggested that more vigorous perioperative infection prophylaxis is needed for titanium plate cranioplasty. Copyright © 2012 by the Congress of Neurological Surgeons.