Objective To propose a personalized design of anatomic ankle prosthesis that can avoid and reduce the high failure rate and risk of ankle prosthesis in clinic. Methods The 3D finite element non-linear model of normal human ankle system was established and verified. The anatomic ankle prosthesis was then designed to simulate total ankle replacement, and the 3D finite element model with both the prosthesis and ankle system was established. The biomechanical characteristics of this prosthesis were calculated and analyzed after gait loads were applied. Results For the normal ankle system, the maximum plantar contact stress was 214.6 kPa and the maximum Von Mises stress of foot bone was 8.96 MPa. The reliability of the normal ankle system model was verified by comparing the simulated results with those reported by literature. After the prosthesis implantation, the simulated maximum Von Mises stresses of talus prosthesis, tibial UHMWPE liner, tibial prosthesis were 23.88, 19.24 and 73.01 MPa, respectively. The stress of the ankle prosthesis increased drastically compared with that of normal ankle system. Conclusions The comparison results by finite element analysis examine the feasibility of the personalized ankle prosthesis, and provide references for optimization of prosthesis design and its clinical application.