A thermodynamic analysis of the Ti-Zr-H ternary system has been performed by combining first-principles calculations with the CALPHAD approach. To enable the thermodynamic description of the binary systems, the results from our previous evaluation were adopted for the Ti-H, Zr-H, and Ti-Zr systems. The ternary compound, Ti2ZrH4, with an Fd3m-type crystal structure, exists over a wide composition range, and the (Ti)2(Zr)1(H,Va)4-type three-sublattice model was applied to describe its thermodynamic properties. Because of the lack of experimental information available, the enthalpy of formation of the Ti2ZrH4 phase was evaluated using the Full Potential Linearized Augmented Plane Wave method, and the estimated values were introduced into a CALPHAD-type thermodynamic analysis with some other experimental information. The calculated phase diagrams and the hydrogen isotherms were in good accordance with previous experimental results. Our calculations revealed that the ternary compound decomposes into a bcc and gas phase in the vicinity of 1270 K.