Multi-stage flash distillation (MSF) system modeling involves a number of process variables. An estimation of all these process variables requires both analytical solutions and experimental/field analysis. However, the accurate estimate of variables related to the brine heater operation in a MSF system is very important for a reliable operation of the system. For example, steam operating conditions as well as the brine properties including fouling of the brine heater tubes have a significant effect on the heat transfer characteristics of the brine heater, which in turn influence the distillate output from the system. In this study, the effect of various design as well as operating conditions on the performance ratio (PR), brine temperature and salinity as it leaves the last flash stage are investigated in a once-through system. Increasing the number of stages from 24 to 32 has a significant effect on the PR, it ranges between 79% (for Delta T = 1.5) and 327% (for Delta T = 2.3) for a top-brine temperature of 106 degrees C. This value increase as the top-brine temperature increases. Increasing the stage-to-stage temperature difference increases the water salinity as it leaves the final stage and reduces its temperature that would imply better energy utilization within the plant. Results show that brine side heat exchanger fouling has a significant effect in decreasing the overall heat transfer coefficient, which reduces the production rate as the fouling increases with time. A sensitivity analysis to identify the key parameters, which can have a significant influence on the desalination plant performance, is carried out in an attempt to contribute a better understanding and operation of MSF desalination processes. (C) 2010 Elsevier Ltd. All rights reserved.