The extended scaled-particle theory, based on the work by Hu et al., (1985) (a), is used to correlate and predict the solubility of N2O in mixed solvents over a wide range of temperatures and concentrations. A method for determining the size and energy parameters of molecules is proposed. Twelve solvents (including seven alkanolamines (MEA, AMP, DEA, MDEA, DIPA, TEA, 2PE), three alcohols (ET, EG, PEG), sulfolane and water) are investigated. The Henry’s constants for 12 ternary systems and nine quaternary systems are calculated. Comparison with the experimental results from the literature indicates that the model is reliable for predicting the solubility of N2O in mixed solvent systems without any additional adjustable parameters.