In this paper, a mathematical model for multistage flash (MSF) desalination plants was developed. The model was based on basic principles of physics and chemistry that describe the stages occurring in the desalination process. The input plant parameters that are known to affect the operation of the MSF desalination plant and its performance was taken into account in the construction of the model. These parameters included make-up flow, brine recycle flow, seawater flow, seawater temperature, seawater concentration, top brine temperature (TBT), steam temperature and the plant load. For each stage, the developed model was used for predicting the temperatures of the brine, distillate and cooling brine, and the flow rates of brine outlet and distillate production. The developed model was evaluated with the MSF plant vendor simulation results and its actual operating data. The evaluation indicated that model predictions matched well with the vendor simulation results and the plant operating data. The developed model is sufficiently accurate and model predictions can be relied upon. Therefore, it may be recommended for determining optimum set point of a running MSF desalination plant at different loads to maximize the water production or minimize energy consumption. It can also be used to calculate controller set points for different loads of the plant. Copyright (C) 2011 John Wiley & Sons, Ltd.