Display omitted ► Brewery yeast was used to produce biogas in an upflow granular anaerobic reactor. ► Mixtures up to 1.1v/v% yeast are anaerobically degradable without adverse effects. ► In full-scale operation biogas production increased by 38.5%. ► Up to 16% natural gas were replaced in brewery operation. ► Up to 7% in archeal and a 32% dissimilarity in bacterial community were shown. The anaerobic co-digestion of brewery yeast using granular biomass was studied on the lab, pilot and full-scale. The study shows no adverse effects in the co-digestion of yeast and wastewater in concentrations up to 1.1 (v/v)%. In concentrations up to 2.3% the process is manageable; however, not advisable. In concentrations over 2.8% the process exhibits failure due to the overload with suspended solids. An average specific biogas production of 0.560m3kg−1 of volatile solids was achieved. Full-scale operation with 0.7% yeast concentration showed a 38.5% increase in the biogas production and a 26.2% increase in the organic loading rate, which resulted in an increase of the biomethane/natural-gas substitute ratio from 10% to 16%. The influence of the yeast addition on the structure of the microbial biomass showed up to 7% dissimilarity in the archaeal and a 32% dissimilarity in the bacterial biomass community, which did not present any difficulties.