Thermal steam-explosion is the most extended hydrolysis pretreatment to enhance anaerobic digestion of sludge. Thermal hydrolysis key parameters are temperature (T) and time (t), and the generally accepted values reported from full-scale information are: 150–230 °C and 20–60 min. This study assesses the influence of different temperature–time–flash combinations (110–180 °C, 5–60 min, 1–3 re-flashing) on the anaerobic degradation of secondary sludge through biochemical methane potential (BMP) tests. All the conditions tested presented higher methane production compared to the untreated sludge, and both solubilization (after the hydrolysis) and degradation (by anaerobic digestion) increased linearly when increasing the severity (T–t) of the pretreatment, reaching 40% solubilization and degradation of the particulate matter at 180° C–60 min. However, for the 180 °C temperature, the treatment time impacted negatively on the lag phase. No influence of re-flashing the pretreated matter was observed. In conclusion, thermal steam-explosion at short operation times (5 min) and moderate temperatures (145 °C) seems to be very attractive from a degradation point of view thus presenting a methane production enhancement similar to the one obtained at 180°C and without negative influence of the lag phase.