The contrastive analysis of the selectivity of potential separating agents (SA) sulfolane, dimethyl sulfoxide (DMSO), and N-methyl-2-pyrrolidone (NMP) relative to the components of a 2,2,2-trifluoroethanol (TFE)-isopropanol (IPA) binary azeotropic system in the differential (Rayleigh) distillation process has been carried out. The experimental data show that adding these SAs leads to significant changes of the relative volatility of the components of the separated mixture. For the three-component systems of TFE-IPA-DMSO and TFE-IPA-NMP, secant-line and cross-section experimental data on vapor-liquid equilibrium (VLE) at 96 kPa (720 mm Hg) were obtained. From the results, the binary azeotrope is eliminated by DMSO and NMP by the means of improving volatility of IPA relative to TFE. Hence, DMSO and NMP are effective solvents for separating the TFE-IPA binary azeotropic system. The obtained VLE data have been simulated using Aspen Plus. V. 9.0 software. To estimate the binary interaction parameters of the NRTL and Wilson equations, data on VLE in binary systems of TFE-DMSO and TFE-NMP were obtained.