This paper describes an approach to rapidly and easily calculate the linear solvent strength parameters, namely log k₀ and S, under reversed-phase liquid chromatography conditions. This approach, which requires two preliminary gradient experiments to determine the retention parameters, was applied to various representative compounds including small molecules, peptides, and proteins. The retention time prediction errors were compared to the ones obtained with a commercial HPLC modeling software, and a good correlation was found between the values. However, two important constraints have to be accounted for to maintain good predictions with this new approach: i) the retention factor at the initial composition of the preliminary gradient series have to be large enough (i.e., log k_i above 2.1) and ii) the retention models have to be sufficiently linear. While these two conditions are not always met with small molecules or even peptides, the situation is different with large biomolecules. This is why our simple calculation method should be preferentially applied to calculate the linear solvent strength parameters of protein samples.