Indoor microclimate control is fundamental in greenhouse design, and vent dimensions and positions play a crucial role in natural ventilation management. This research considers an Italian greenhouse for horticultural production and aims at identifying optimal vent configurations and opening management procedures for indoor environment control, focusing on summer cooling. Numerical modelling of airflows and temperature distributions was carried out through finite element CFD software, with streamline upwind discretization schemes for advection terms. Calibration of the numerical modelling was performed by comparing data collected in controlled environmental condition with simulations results. The automatic vent opening system of the greenhouse is programmed to fully open all the windows of each span when indoor air temperature overcomes a threshold value. Numerical simulations were performed to assess the efficacy of this solution in comparison with alternative strategies. Various configurations of roof vents were tested, with side wall vents always open. The best performances were obtained with windward roof vent closed, which entailed 64% of the maximum heat removal achievable through natural ventilation. The other possible scenarios considered showed a performance index of about 50%. The results suggest therefore to enhance the vent control system by considering also wind direction as input. (C) 2016 Elsevier B.V. All rights reserved.