The metastable β-type Ti-12Mo-6Zr-2Fe alloy was subjected to an assessment of its fatigue mechanical behavior. Promising tensile and fatigue properties were obtained when the alloy was solution treated and quenched, because nanocrystalline particles of ω phase were formed throughout the β matrix. When the material was subjected to a protocol of chemical etching and a subsequent surface polishing, the fatigue limit decreased significantly as a result of H pick-up, although the tensile properties were not changed. The increase of the local H concentration caused the precipitation of fine hydrides at high-energy grain boundaries. Fatigue crack initiation changed to a subsurface mode induced by the cleavage of hydride precipitates.