Fatigue resistance, particularly the endurance limit, is an important design consideration in engineering applications for TiZr-based alloys. The investigated Ti-20Zr-6Al-4 V (wt-%) alloy exhibited a high fatigue endurance limit of 775 MPa. Results showed that severe local stress concentration due to extensive dislocation pile-up at α/β interfaces was responsible for the crack initiation. A transition from a tensile mode to a shear mode crack was observed during crack propagation. Many striations as well as some micro-cracks which can improve the resistance to crack propagation exist in the stable crack-propagation region. A localised deviation between the crack-growth direction was also found, and this outcome combined with micro-cracks and tear ridge may be attributed to varied crystallographic orientations between different phases.