BACKGROUND: A novel, bioactive, fiber-reinforced composite implant is a solution to address the shortcomings in craniofacial bone reconstruction. A longitudinal clinical investigation with a follow-up time of 4 years was conducted. METHODS: A cranial bone reconstruction with the implant was performed on 12 patients. In these patients, the reasons for craniotomies resulting in craniofacial bone defects were traumatic and spontaneous intracranial bleeding as well as infections to the primary reconstruction material. The implant material consisted of a supporting fiber-reinforced framework, porous inner layers, and a bioactive glass (BG; S53P4) filling. The framework and the porous layers were made of a bisphenol-a-glycidyl methacrylate and triethyleneglycoldi-methacrylate (pBisGMA-pTEGDMA) resin matrix, which was reinforced with silanized E-glass. RESULTS: In clinical examinations and skull X-rays, the implants were in original positions providing the expected functional and aesthetic outcome at all time points. CONCLUSION: The implants functioned appropriately, which would provide a potential solution for craniofacial bone reconstruction in the future.