Abstract Background Different methods of cranioplasty for the reconstruction of bony skull defects exist. In the absence of the autologous bone flap, a customised manufactured implant may be the optimal choice, but this implant has several limitations regarding its technical standardisation and better cost-effectiveness. Methods This study presents a series of 16 consecutive patients who had undergone cranioplasty with customised three-dimensional (3D) template moulds for polymethylmethacrylate (PMMA) implants manufactured after 3D modelling on a specific workstation. The virtual images were transformed into a two-piece physical model using a 3D printer for the biomaterials. PMMA implant was produced intraoperatively with the custom mould. Cosmetic results were analysed by comparing pre- and postoperative 3D computed tomography (CT) images and asking if the patient was satisfied with the result. Results The average total time for planning and production of customised mould was 10 days. The 16 patients were satisfied with the result, and CT images presented harmonious symmetry when comparing pre- and postoperative scans. Cases of postoperative infection, bleeding, or reoperation in this series were not observed. Conclusion Cranioplasty with high-technology customised 3D moulds for PMMA implants can allow for an aesthetic reconstruction with a fast and cost-effective manufacturing process and possibly with low complication rates.