Microstructural evolution of anode supported solid oxide fuel cells (SOFC) during medium-term stack testing has been characterized by scanning electron microscopy (SEM). Low acceleration voltage SEM imaging is used to separate the three anode phases (nickel, yttria-stabilized zirconia and porosity). Microstructural quantification is obtained using a software code that yields phase proportion, particle size, particle size distribution and a direct measure of triple phase boundary (TPB) density. In addition, an anode degradation model is proposed. The model describes the gradual degradation of the anode due to nickel particle sintering and the concomitant loss of TPB. Fundamental operational and structural parameters of the anode can be used to estimate the TPB length change with time from the degradation rate. The combination of experimental results and modeling allows separating the degradation due to sintering of nickel particles from total stack degradation. Anode degradation occurs principally during the first 500 operating hours. For stack tests carried out over more than 1000 h, anode degradation was responsible for 18 % to 41 % of the total degradation depending on initial microstructure.