Abstract At present, the analysis of the performance of air handling units based on desiccant wheels is a complex task for a HVAC&R designer. It is difficult to access a simple model that can represent, with enough accuracy, the behaviour of commercialized desiccant wheels operating with variable inlet states and variable airflows. This work is devoted to investigate the feasibility of a simplified simulation method based on the effectiveness concept. Additionally, an analysis is made of the appropriateness of using a new pair of independent effectiveness parameters instead of the classical approach based on the combined potentials. The first running tests performed with two manufacturers’ software and with a detailed numerical model show that the airflow inlet states have a non negligible influence on the effectiveness parameters. As expected, it is also observed that the effectiveness parameters depend strongly on the airflows rates. So, the effectiveness method based on constant values is not recommended to be used in practise. A new approach using 2D linear interpolation on an irregular grid to take into account the effectiveness dependence on the inlet states of both airflows is presented. A correlation of exponential type is proposed for predicting the effectiveness parameters in case of variable balanced airflows rates, and it is subsequently tested either separately or combined with 2D linear interpolation approach. The proposed methodology requires a reduced amount of data to model a given desiccant wheel, and the predicted results evidence good accuracy. This approach can be used with great advantages in the generalised dynamic analysis of systems integrating a desiccant wheel including the effects of variable inlet states and of variable balanced airflows rates.