As the performances of Solid Oxide Fuel Cells (SOFC) get attractive, long term degradation becomes the main issue for this technology. Therefore it is essential to localise the origin of degradation and to understand its mechanisms in order to find solutions and to improve SOFC durability. Microstructural evolution of anode supported solid oxide fuel cells (SOFC) during medium-term stack testing has been characterized by scanning electron microscopy (SEM). A new technique is presented using low acceleration voltage SEM imaging to separate the three anode phases (nickel, yttria-stabilized zirconia and porosity). Microstructural quantification is obtained using a software code that yields phase proportions, particle sizes, particle size distribution and a direct measure of triple phase boundary (TPB) density (μm/μm3). In addition, an anode degradation model is developed. It describes the gradual degradation of the anode due to particle sintering and the concomitant loss of the three-phase-boundary. Fundamental, operational and structural parameters of the anode can be used to estimate the three-phase-boundary length evolution 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 medium term stack operation (more than 1000 h), anode degradation is responsible for 18 % to 46 % of the total degradation depending on stack technology.