The chromatographic behavior of ivabradine have been examined using Kieselgel 60 F254, 60 W F254S, and RP-18 W F254S high performance thin layer chromatography (HPTLC) plates as stationary phases. Mobile phases were wide-ranging mixtures (from 0%to 100%, v/v)—non-aqueous and buffered binary mobile phases. Chromatographic retention data and possible retention mechanism were discussed. The electrostatic interactions operating in these chromatographic systems were analyzed by studying the relationship between the log (1/RF ) values and the molecular polarizabilities of solvents as well as the thermodynamic dependence has been shown. Enthalpy and entropy results were calculated from regression coefficients (a, b) and Van't Hoff plot. Gibbs free energy was calculated in accordance with the definition. The influence of the molecular polarizability of the mobile phase on the retention of ivabradine was also examined.