A variable-gain controller for anaerobic digestion of industrial winery wastewater was examined. A control law using both volatile fatty acids (VFA) and CH 4 production rate as controlled variables and organic loading rate (OLR) as manipulated variable is defined. The process state is quantitatively estimated by an empirical function comparing VFA measurements against a setpoint value and then modified with a second empirical function that compares the CH 4 flow rate with a maximum capacity reference. Finally, it is adjusted with a third factor considering the actual hydraulic retention time. The variable-gain function determines the extent of the OLR change applied to the system. The controller was successfully validated in a 95 L upflow-anaerobic-sludge-blanket (UASB) reactor, treating industrial wine wastewater at OLR ranged between 2.0 and 39.2 g COD/L-d for 120 days at mesophilic conditions. Higher performance was achieved contrasted with a conventional strategy carried out in a parallel UASB unit.