In this study, an advanced process based on the use of ultrafiltration hollow fibre membranes immersed in the supernatant of an upflow anaerobic sludge blanket bioreactor (MUASB) and operated under low permeate flux was proposed. Process sustainability was assessed under different operating conditions: membranes were immersed either in the supernatant or in the biomass bulk and operated under various permeate fluxes. Additionally, temporal investigation was also proposed through the advanced characterization of fouling behaviour by systematic fractionation (based on level of reversibility) and analysis by liquid chromatography-organic carbon detector. Among the various suspended solids (SS) concentrations in supernatant (10, 25, 100, and 400 mg L(-1)) and in biomass bulk (6500 mg L(-1)), higher fouling levels were observed under low SS concentrations. However, more easily reversible fouling was obtained under MUASB conditions, demonstrating potential long-term sustainability. Results of long-term operation indicated that an increase of flux leads to larger amounts of SS participating in irreversible fouling and higher irreversibility. Temporal change in fouling characteristics revealed that the most easily removable fouling layer (i.e. cake), and its relative fraction of SS, were the two main factors impacting on the overall hydraulic performance. Additionally, the development of microbial population on the membrane surface was closely related to the proteins content and the overall hydraulic resistance. Polysaccharides and other dissolved organic matters (humic substances, building blocks, and low molecular weight compounds) presented low effect on membrane fouling.