This paper presents the study of the variations of the process parameters during transient conditions when substrates with different biodegradability were fed to a pilot-scale anaerobic digester. The two substrates used in the experiments were the mechanically selected organic fraction of municipal solid wastes and a blend of mechanically selected and separately collected organic fraction of municipal solid wastes. Two transient conditions were studied: the mesophilic-thermophilic passage and the increase of the organic loading rate in thermophilic conditions. It was shown that enhanced fractions of biodegradable substrates determined a greater perturbation of the system and needed longer time to reach a new stable condition. The volatile fatty acids concentration and their indirect measure, alkalinity determined upon pH 4, was the more useful parameter to understand the process behaviour because of its sensitivity to the process variations.