A mathematical model able to describe the operation of a GSBR was successfully calibrated and validated. The subsequent model exploitation revealed that N-removal was always enhanced when the DO applied produced a slight ammonium accumulation in the effluent (e.g. 5 mg N–View the MathML source L−1). Furthermore, this occurred independently of granule size, influent C/N ratio or NLR. Accordingly, we proposed a cascade ammonium and oxygen control strategy that successfully automates finding the adequate DO concentration to enhance N-removal. The control strategy will set the appropriate DO set-point at whatever values of granule size, influent C/N ratio or NLR. Therefore, high N-removal efficiencies (between 70% and 85%, in most cases) will be assured by the control strategy against disturbances in those variables, which are common during the reactor operation. This is one of the first control strategies proposed for aerobic granular reactors and future research in pilot plant to confirm these results would be desirable.