This work gives a van’t Hoff law expression of Langmuir constants of different species for determining their occupancy in clathrate hydrates. First, a pairwise site–site interaction potential energy model is used to calculate the Langmuir constants in an otherwise anisotropic potential environment, as a function of temperature. The results are then fitted to a van’t Hoff law expression to give a set of parameters that can be used for calculating clathrates compositions. The van’t Hoff law’s parameters are given for eighteen gas species trapped in the small and large cavities of structure types I and II. The accuracy of this approach is based on a detailed comparison with available experimental and/or previously calculated data for ethane, cyclo-propane, methane and carbon dioxide clathrate hydrates. A comparison with the analytical cell method is also carried out to better understand the importance of asymmetry and possible limitations of the van’t Hoff temperature dependence.