This work provides detailed knowledge of long-term deactivation of Ni catalysts in CO2 methanation. NiAlOx mixed oxides with varying Ni loading as well as a 17 wt-% Ni/y-Al2O3 catalyst were synthesized via co-precipitation and incipient wetness impregnation, respectively. The catalysts were aged at 523, 573 and 623 K under equilibrium conditions up to 165 h. Periodic activity measurements under differential conditions reveal severe deactivation. The stability of co-precipitated systems increases with decreasing Ni content on the expense of catalyst activity. Ni/gamma-Al2O3 exhibits a lower stability as a comparable mixed oxide. A power law model is applied for the kinetic description of deactivation. Catalyst samples are characterized by means of temperature programmed desorption of H-2 (H-2-TPD) and CO2 (CO2-TPD), pulsed H-2 chemisorption, XRD, FT-IR spectroscopy, XPS and N-2 physisorption. Main deactivation mechanisms in the co-precipitated samples are found to be Ni particle sintering, a loss of BET surface area as well as a reduction of CO2 adsorption capacity and medium basic sites, along with structural changes of the mixed oxide phase. Ni particle growth and a decrease in BET surface area lead to deactivation of the impregnated sample. Structure-activity correlations imply a complex interplay of governing deactivation phenomena as well as structure sensitivity.