Anaerobic digestion of food waste and distillers' grains with ethanol pre-fermentation (EP) at different inoculum-to-substrate ratios (ISRs) was investigated. With EP, the highest methane yield of 581.2 mL/g-VS was observed at ISR 2.5, with the methane yields of ISR 1.0 and ISR 0.4 being 41.8% and 71.7% lower. At the same ISR, the methane yield without EP (control group) was 143.2 mL/g-VS, 57.7% lower than that with EP. EP effectively alleviated inhibition by acidification, greatly reduced the duration of the lag phase, and markedly stimulated the growth of methanogens, compared with that of the control group. Thermodynamics analysis of various acidogenic fermentation patterns suggested that directing the acidogenic phase towards ethanol, instead of towards volatile fatty acids, allocates more potentially available energy for methanogens. Thus, EP prior to anaerobic digestion is a suitable way to stabilize an anaerobic digestion system even at a low ISR. (C) 2015 Elsevier Ltd. All rights reserved.