We determined the excess partial molar enthalpy and the excess partial molar volume, HTFEE, VTFEE, of 2,2,2-trifluoroethanol (TFE) in TFE-H2O at 25.0 °C. We then evaluate the TFE-TFE interactions in terms of enthalpy and volume, HTFE-TFEE and VTFE-TFEE, graphically without resorting to any model dependent fitting functions. Both model-free third derivatives indicate that TFE is a hydrophobic solute and that as other hydrophobic alkyl mono-ols there are three distinct mixing schemes, Mixing Schemes I, II, and III in their aqueous solutions. The relative strength in hydrophobicity between TFE and tert-butylalcohol (TBA), for example, gave a mixed message within the behavior of these third derivative quantities. We thus applied the 1-propanol (1P) probing methodology (Koga, Y. Phys. Chem. Chem. Phys. 2013, 15, 14548) that utilizes the fourth derivative in effect, and quantified the degree of hydrophobicity of TFE. It turned out that TFE is a stronger hydrophobe than 1P and ethanol (ET), and has approximately the same hydrophobicity as TBA within the estimated uncertainty. These findings were compared with the ability reported in literature to denature β-lactoglobulin and to induce α-helices in melittin in their aqueous solutions.