Biorefinery represents an innovative approach for waste management, where products at the end of their service life are seen as valuable resources for the production of high added value bio-products or bio-fuels. In this context, acidogenic fermentation is gaining scientific and commercial interest, since it allows to improve waste/wastewater treatability as well as additional recovery of volatile fatty acids (VFA), the building blocks for the chemical industry or precursors of reduced chemicals in conventional organic chemistry. This work illustrates the results of a study aimed at highlighting the effects of different inputs (feedstock composition and pre-treatment; temperature) on process performance and safety. The fermentation process was applied on a mixture of food waste and sewage sludge (FWs-SS) within the contest of Treviso municipality (northeast Italy). The VFA production and relative ratio respect to soluble chemical oxygen demand (CODSOL) were evaluated, as well as the variation of lower flammability limit (LFL) of flammable gaseous mixture, produced during the acidogenic fermentation. Thermal pre-treatment (72°C, 48 h) enhanced the solubilization of the organic matter, which was converted into VFA in batch mode under mesophilic conditions (37°C). The VFA level increased up to 30 ± 3 g COD/L, with high CODVFA/CODSOL ratio (0.86 ± 0.05). This condition was also characterized by the lowest level in volumetric percentage of flammable gases such as H2, CH4 and H2S. Variation of LFL of gaseous mixture as function of fermenter operating parameters has been investigated by Le Chatelier’s Law. The high concentration of CO2 (greater than 80% v/v) increased the LFL and therefore the flammable mixture was considered poorly hazardous. In practice, the variation of fermenter operating parameters to the final optimized protocol caused a continuous LFL growth, up to 29.3%, corresponding to a safer operation of fermentation reactor.