In this work, volumetric properties and UV−visible spectroscopic analyses were performed to investigate the kind of interactions occurring among thiamine hydrochloride (Th.HCl) and protic ionic liquids (PILs) in aqueous solutions at temperatures (298.15−313.15 K) and at 0.1 MPa. Interactions between drug molecule and three PILs (namely, ethanolammonium acetate, EAAc, ethanolammonium butyrate, EABu, and ethanolammonium hexanoate, EAHx) were evaluated. Density, ρ, and speed of sound, c, of Th.HCl in water and in mixed aqueous solutions of three PILs with concentrations (0.05, 0.10, 0.15, and 0.20) mol kg −1 were measured at different temperatures. Further, using these experimental values, apparent molar volumes, apparent molar isentropic compressibilities, and volumetric transfer parameters were calculated to understand and infer the interactions. Positive transfer volumes indicate the presence of hydrophilic interactions, whereas the negative transfer volumes observed indicate the presence of hydrophobic interactions among the components of PILs (cations/ anions) and Th.HCl. The presence of hydrogen bonding interactions was indicated by a hyperchromic shift in the UV−visible absorption spectra of the ternary solutions.