A model is proposed to describe the mechanical behavior and the ductile failure at 25, 350 and 480°C of Zircaloy-4 cladding tubes, as-received and hydrided up to 1200wt. ppm (circumferential hydrides). The model is based on the Gurson–Tvergaard–Needleman model extended to account for plastic anisotropy and viscoplasticity. The model considers damage nucleation by both hydride cracking and debonding of the interface between the Laves phase precipitates and the matrix. The damage nucleation rate due to hydride cracking is directly deduced from quantitative microstructural observations. The other model parameters are identified from several experimental tests. Finite element simulations of axial tension, hoop tension, expansion due to compression and hoop plane strain tension experiments are performed to assess the model prediction capability. The calibrated model satisfactorily reproduces the effects of hydrogen and temperature on both the viscoplastic and the failure properties of the material. The results suggest that damage is anisotropic and influenced by the stress state for the non-hydrided or moderately hydrided material and becomes more isotropic for high hydrogen contents.