BACKGROUND: Biocompatible computer-assisted design (CAD) implants for cranioplasty are associated with high costs and considerable waiting time. We present the results of the first cranioplasty experience in our country using polymethylmethacrylate (PMMA) with customized 3D molds of the cranial defect. METHODS: We present a case series describing five patients with extensive cranial defects who underwent cranioplasty with PMMA using customized 3D molds. From tomographic studies, a bone implant model for the cranial defect was virtually designed and a mold was built according to the specifications of the defect. The mold was printed in 3D using acrylonitrile-butadiene-styrene. With the sterile mold, the implant could be designed intraoperatively with PMMA to perform the cranioplasty. The evolution, complications, and cost of the implant were evaluated. RESULTS: No postoperative complications were observed. Good aesthetic and functional results were achieved in all patients. The cost of the implant per patient using our technique was approximately 50 USD. In our country, the cost of CAD implants varies between 0000 and 0000 USD. CONCLUSIONS: Cranioplasty with PMMA and 3D custom mold is a safe and low-cost technique that would benefit patients in middle- and low-income countries. Compared to CAD implants, the cost was reduced by 95%-97%. This technique can be implemented on a large scale with remarkable benefits in low- and middle-income countries.