Operation and performance of membrane bioreactors (MBRs) for wastewater treatment is influenced by changes in activated sludge properties. Therefore, understanding of the factors influencing sludge filterability is of major importance for efficient operation of MBR installations. This paper assesses the impact of the influent characteristics on activated sludge filterability and treatment performance of full-scale MBRs. The full-scale MBRs were closely monitored both in summer and winter. The measurement campaign, consisting of activated sludge filterability tests and physicochemical analyses, is supplemented with operational performance data evaluation of the various full-scale plants. Based on these data, it is shown that an undesired and refractory composition of incoming wastewater, hydraulic and/or organic load shocks, as well as abrupt temperature changes of the influent, lead to operational problems and affect sludge filterability.