Oxic-settling-anaerobic (OSA) process has been introduced into the treatment line of wastewater in order to upgrade activated sludge processes and to reduce the production of excess sludge. The aim of the present study was to simulate the performance of an OSA pilot plant by implementing the Activated Sludge Model No.2d (ASM2d) into a mathematical modelling software (BioWin). The stepwise calibration, performed both by off-line experiments and software dynamic calibration, was carried out in a heuristic way, adjusting the parameters values that showed a major influence to the effluent and internal concentrations. All the reduction factors introduced into ASM2d to simulate the processes occurring in anoxic and anaerobic conditions were lowered in order to reproduce the concentrations of interest. In addition, the values of parameters of the PAOs (polyphosphate accumulating organisms)-related process (namely qPHA and YPO4) were found lower than those usually adopted. In general, theoretical results were in good agreement with the experimental data obtained from plant’s operation, showing an accurate predictive capacity of the model. Good performance was achieved considering the phosphorus removal related process, while some failures were detected in COD and ammonia simulations.