The weakness of nickel-based solid oxide fuel cell anodes is their low ability to withstand re-oxidation at working temperature, especially for the anode-supported cell design. The volume expansion coming along with nickel (Ni) oxidation induces stresses in the layers and cracks especially for the thin supported electrolyte. Standard Ni-yttria stabilized zirconia (YSZ) anode-supports and half-cells (anode + electrolyte) were studied during repeated reduction and oxidation cycles (RedOx cycles) at different scales and different temperatures. The nanometer scale observations point out that the internal porosity built up during nickel oxidation is the main reason for RedOx instability. This porosity arises from the Kirkendall effect during nickel oxidation. High temperature re-oxidation increases the internal porosity and thus the volume expansion of the anode. At the micrometer scale, the variation of electrolyte cracks and anode porosity could be related to linear expansion of the support. Linear expansion reaches a plateau after more than 10 RedOx cycles and a RedOx-"safe" temperature of 550 °C could be defined for this microstructure. At the macroscopic scale, the curvature towards the anode half-cell increases during a high temperature RedOx cycle. This increases RedOx instability and is related to the inhomogeneous re-oxidation of the anode across its thickness. The curvature change arises from non-elastic and non-homogeneous deformation of the support during re-oxidation. A Design of Experiment with Surface Response Methodology approach was used to optimize new microstructures for RedOx stability, electrical conductivity and sinterability of anode-supported SOFCs. The major anode internal parameter enhancing RedOx stability is the porosity. Some microstructures show RedOx stable anodes with a rather low 35 % as-sintered porosity, but with 50 % as-sintered porosity, any microstructure is believed to be RedOx stable. Three new different anode compositions, containing from 40 to 60 wt% NiO were produced by tape-casting and tested over more than 10 full RedOx cycles at 800 °C. The electrochemical tests show a constant open circuit voltage (OCV) and about 1 %/cycle of performance degradation between 0.4 and 0.5 Wcm-2 at 0.6 V and 800 °C. The electrical conductivity and electrochemical performance degradations versus time are important during the first reduction but are stabilized after multiple RedOx cycles. The nickel coarsening is limited after multiple RedOx cycles due to the pinning by small zirconia particle inclusions. An anode supported cell 55 cm2 in size with optimized microstructure was implemented in SOFC stack configuration and tested over 50 RedOx cycles. While the performance was nearly constant, the OCV decreased by only 0.1 %/cycle. The performance was three times lower compared to small cells, but shown to be due to poor electrical contact and limiting fuel flow and composition in the employed stack assembly.