This study investigates the efficiency in methane production of lab-scale mesophilic (37 degrees C) and thermophilic (54 degrees C) continuous stirred tank reactors fed with cheese whey at different operational conditions. Results showed that whey mono-digestion was feasible at mesophilic conditions, while at thermophilic conditions frequent acidification incidents were recorded. The limited buffer capacity of the influent feedstock was responsible for the unstable anaerobic digestion process. The co-digestion of cheese whey with cattle manure maintained the pH levels higher than 7.0, and therefore, stable methane production rates were achieved without any significant accumulation of volatile fatty acids. An additional enhancement of the methane productivity was achieved by in-situ H-2 dispersion. Microbial community composition was investigated using high-throughput 16S rRNA gene amplicon sequencing and results were correlated with process parameters. Hydrogenotrophic methanogens were the dominant archaea during the whole experiment at mesophilic and thermophilic conditions.