Statistical Thermodynamics was used to derive an expression for hydrate enthalpy of dissociation. From this expression, a parameter regression methodology was proposed in which calorimetric experiments were included along with cage occupancies, guest mole fraction and equilibrium condition experiments. Since not all the experiments depend on the whole set of hydrate parameters, we developed a stepwise methodology that reduces hydrate estimation problem to three simple sub problems, being two of them analytically solvable. The solution of the stepwise methodology is then the initial guess of the hydrate global parameter estimation that can be solved using a deterministic algorithm. From the parameter estimation, we observed that the hard-core sphere parameter of the Kihara potential was not statistically significant in the case studied here. It was rejected with a significance degree of 5%, which lead to the use of the Lennard-Jones potential. After estimating hydrate parameters for carbon dioxide and methane sI hydrates, we could relate hydrate enthalpy of dissociation to equilibrium conditions for this binary mixture. We found that the empirical law that states that enthalpy of dissociation of mixed hydrates increases with the increase of occupancy of the largest guest in the large cavity was verified only when the water-poor fluid phase is a vapor. This means that fluid phases also have an important role in hydrate enthalpy of dissociation. (C) 2017 Elsevier Ltd.