Background: Cranial reconstruction is a common consequence of neurosurgical disease and intervention following craniectomy, trauma, infection, congenital defects, or neoplasm. Most commonly, Computer Aided Design-Computer Aided Manufacturing (CAD-CAM) technology is utilized in cases where autologous bone cannot be used. These patient-specific implants provide excellent cosmesis, however individual costs range from $800-15,000, making routine use challenging in the current Canadian health care environment. Here we present a novel method using desktop 3D printers to manufacture patient-specific molds for intraoperative reconstruction of various cranial defects. Methods: Our first patient presented following two separate traumas requiring decompressive craniectomy and subsequent posterior fossa decompression without interval cranioplasty. The second patient required reconstruction during resection of intraosseous meningioma. Both cases were performed using a titanium-mesh/poly-methyl-methacrylate (Ti-PMMA) construct draped over the mold. The third case, cranioplasty following decompressive craniectomy outside the country, was performed using a “two piece” mold and PMMA was casted into the mold and allowed to harden. Results: Patients reported satisfaction with cosmesis, without adverse outcomes. Cost per case was $50-100, representing an estimated cost savings of $685,000 per year in Canada. Conclusions: Given excellent outcomes in addition to cost effectiveness, this case series provides evidence for use of this alternate technique with similar patient outcomes.