In this paper the operation of an Academic Hospital installation is evaluated by simulation and optimization on a yearly base. A mathematical model has been developed, which is based on energy balances of the installed components. Manufacturer specifications of the components are used for calculating the parameters. The model is formulated using vector equations. Advantages of this type of model formulations are presented. The tools used for optimization are custom developed back-tracking methods for calculating a good starting point and a SQP optimization tool for finding the optimum. Detailed control strategies are calculated for three types of optimization strategies simulated. The simulation results show the impact of the choice of a control strategy on the optimized operation. The results are also applicable for on-line setpoint optimization.