PURPOSE: The auxetic porous bone screw (AS) has favorable anti-pullout and osseointegration performance, demonstrating application potential in orthopedic surgeries. The uniaxial fatigue behavior of AS has been well understood. Considering that AS will withstand complex physiological loads in practical application, this study aims to investigate the fatigue behavior of AS under the multiaxial loads in tibiotalocalcaneal arthrodesis. METHODS: AS and nonauxetic bone screw (NS) with the same porosity were designed based on re-entrant and hexagonal units, respectively. Finite element models of tibiotalocalcaneal arthrodesis implanted with AS and NS were established. Based on the curves of ground reaction forces borne by foot during normal gait cycle, the multiaxial loading spectrums were created and applied to the models. The multiaxial fatigue simulations were conducted to calculate the fatigue life and principal stress distributions of bone screws. RESULTS: Under the multiaxial loads in tibiotalocalcaneal arthrodesis, fatigue fracture was prone to occur in the AS and NS implanted in medial calcaneus. The minimum fatigue life and maximum principal stress of AS and NS were all located near the screw caps connected with the fixation plate. The tensile stress concentration of AS was significantly higher. The estimated fatigue life of AS and NS was approximately 46400 and 1820000 cycles, respectively. CONCLUSION: The fatigue life of AS was significantly lower than that of NS, which could not meet the fatigue resistance requirement during the recovery period of tibiotalocalcaneal arthrodesis. Local optimization should be conducted near the screw cap of AS to improve its multiaxial fatigue resistance.