Custom titanium cranioplasty plates, manufactured by a variety of techniques, have been used to repair a range of cranial defects. The authors present a case where two relatively large, adjacent cranial defects were repaired by custom computer-designed titanium plates. The two plates were designed and fabricated simultaneously using a unique methodology. A 28-year-old woman underwent a corpus callosotomy for medically intractable epilepsy. The surgery was complicated by unexpected haemorrhage which necessitated a second craniotomy. Subsequent deep infection required the removal of bilateral bone flaps, presenting a challenge in the reconstruction of extensive, bilateral but asymmetrical cranial defects. The patient underwent a head computed tomography scan, from which a rapid-prototype model of the skull was produced. The surfaces for the missing cranial segments were generated virtually using a combination of software products and two titanium plates that followed these virtual contours were manufactured to cover the defects. The cranioplasty procedure to implant both titanium cranial plates was performed efficiently with no intra-operative complications. Intra-operatively, an excellent fit was achieved. The careful planning of the plates enhanced the relative ease with which the cranial defects were repaired with an excellent cosmetic outcome.