Optimal control strategies have been developed to enhance the performance of ventilated cavity walls (VCWs) with spray evaporative cooling systems. In particular, the spray system and three dampers are operated to regulate water usage and cavity air flow in order to maintain indoor thermal comfort, reduce water usage, prevent mold growth risk, and minimize cooling energy consumption. The control strategies have been obtained through multi-objective optimization analysis using genetic algorithm search technique. In particular, it is found that the spray droplet size can be used as a control variable to effectively operate the VCW systems. For residential buildings in Riyadh, it is found that 30 mu m droplets provided the best compromise between indoor thermal comfort, water use, and mold growth potential. The optimal control strategies have been obtained through two approaches: (i) long-term (i.e., one season or one year) optimization based on both outdoor and indoor conditions with a fixed droplet size, and (ii) short-term (i.e., one hour or one-day) optimization that includes the droplet size as a control variable in addition to outdoor and indoor conditions. Using the first approach, the optimal control strategies of buildings equipped with VCWs are found to be able to reduce cooling energy consumption by 23% compared to that used by buildings having conventional concrete walls. The second optimization approach indicates that VCW system is able to provide 100% cooling energy savings compared to the conventional walls. Moreover, the optimum control strategies for VCWs have found to reduce water usage by 78% and mold growth by 98% while maintaining indoor thermal comfort when compared to uncontrolled VCW system. (C) 2017 Elsevier B.V. All rights reserved.