The functionality of a denture is directly related to the quality of life of the edentulous patients because treatment failure results in demoralizing consequences including difficulties in oral activities. Framework for fixed complete dentures plays a crucial role by transferring loads from the denture to the implants, which are integrated into the remaining bones and gingiva, thereby providing stability to the denture. Current techniques utilize 3D scan data of the implant site to capture the locations and soft tissue contours to design customized framework using computer-aided design (CAD) and computer-aided manufacturing (CAM) technology to properly support the denture teeth in their position. The performance and efficiency of these frameworks may be enhanced by incorporating a design optimization in the design process. We tested the feasibility of using the topology optimization to design patient-specific dental frameworks.The shapes of the optimized frameworks may be significantly different from the traditional designs, but better structural integrity is likely to be achieved with potentially less material. The numerical study reveals that commercially available dental framework would experience 16% less maximum stress when topology optimized even with a compliance minimization formulation with 50% volume fraction constraint. Topology optimization for designing dental frameworks might improve current clinical methods and provide better long-term patient satisfaction. KEYWORDS denture framework, 3D printing, topology optimization Int J Numer Meth Biomed Engng. 2019;35:e3193.wileyonlinelibrary.com/journal/cnm