Due to the large reversible strains achievable through the stress-induced austenite-martensite phase transformation in NiTi alloys, NiTi has replaced stainless steel in the majority of large-strain biomedical applications such as root canal enlargement. However, the pseudoelasticity of NiTi is currently overshadowed by the short fatigue life of NiTi wires used in this low cycle (200 -2000 rpm), high amplitude ( a > 2.5%) application, resulting in in vivo fracture or premature retirement of otherwise reusable NiTi-based wire devices. In this study, the failure of pseudoelastic 55.8 wt % Ni-Ti wire is investigated experimentally, as a function of experimental parameters that include the clinically relevant regime. The effects of radius of curvature, angle of curvature, wire diameter, strain amplitude, cyclic frequency, volume under strain, and specific heat of the surrounding environmental fluid are considered systematically. These data indicate that the lifetime or cycles to failure N f of a rotating NiTi wire can be predicted via a modified Coffin-Manson relation that is a strong function of both strain amplitude and volume under strain, and a weaker function of frequency and fluid specific heat. The resulting quantitative relation can be used to predict useful device lifetime under clinically relevant conditions and thereby reduce incidences of in vivo failure.