Zr3Fe and Ni-substituted Zr3Fe alloys with 30 and 50 at.% Ni were synthesized and their hydrogen absorption/desorption characteristics were compared experimentally (pressure–composition isotherms, thermal desorption spectroscopy, in-situ neutron diffraction) and by computational methods (ab-initio molecular dynamics (AMD), nudged elastic band theory (NEB)). All the alloys absorbed hydrogen to a hydrogen-to-metal atomic ratio of about 1.7, but the hydrides formed were stable at room temperature. The Zr3Fe0.5Ni0.5 alloy and its hydrided form were multi-phase. The Zr3Fe0.7Ni0.3 alloy was single-phase and retained the structure of the parent intermetallic. In-situ neutron diffraction with D2 in place of H2 showed that the hydride formed in the isotherm measurements, Zr3Fe0.7Ni0.3H6.88, had the same structure (Cmcm) as Zr3FeH7, while disproportionation was observed in the hydrogenation of Zr3Fe. The kinetics of hydride formation was slower in both the Ni-substituted alloys. Thermal desorption spectroscopy showed that substitution of 0.3Ni significantly destabilized the hydride, lowering the temperature of the principal desorption peak by about 300 K relative to Zr3Fe–H2, without loss of hydrogen capacity, and avoiding disproportionation. Based on the structures determined by neutron diffraction, AMD and NEB calculations were conducted to compare Zr3Fe and Zr3Fe0.7Ni0.3 and their hydrides. The AMD calculations predicted that H diffusion was slower in Ni-substituted Zr3Fe, in agreement with the experimental observation of slower kinetics, implying a higher activation energy for H migration. The NEB calculations also predicted a higher energy barrier for H migration in Ni-substituted Zr3Fe.