Cattle manure is an agricultural residue, which could be used as source to produce methane in order to substitute fossil fuels. Nevertheless, in practice the handling of this slowly degradable substrate during anaerobic digestion is challenging. In this study, the influence of the pre-treatment of cattle manure with pressure-swing conditioning (PSC) on the methane production was investigated. Six variants of PSC (combinations of duration 5 min, 30 min, 60 min and temperature 160 °C, 190 °C) were examined with regards to methane yield in batch tests. PSC of cattle manure showed a significant increase up to 109% in the methane yield compared to the untreated sample. Kinetic calculations proved also an enhancement of the degradation speed. One PSC-variant (190 °C/30 min) and untreated cattle manure were chosen for comparative fermentation tests in continuously stirred tank reactors (CSTR) in lab-scale with duplicates. In the continuous test a biogas production of 428 mL/g volatile solids (VS) (54.2% methane) for untreated manure was observed and of 456 mL/g VS (53.7% methane) for PSC-cattle-manure (190 °C/30 min). Significant tests were conducted for methane yields of all fermentation tests. Furthermore, other parameters such as furfural were investigated and discussed.