Herein were performed theoretical and experimental studies about the performance of the cationic surfactant docecyltrimethylammonium chloride (C12TAC) on the enhancement of the oil recovery factor (ORF) from heavy oil-impregnated calcite cores. The interaction energies between C12TAC and either of some molecules present in oil such as an asphaltene (Asph), a resin (Res) or an octanoic acid, and among these and a calcite surface were theoretically determined within the framework of the Density Functional Theory. Experimental analysis based on Fourier transform infrared (FTIR) spectroscopy as well as 1H and 13C nuclear magnetic resonance (NMR) spectra were made on the heavy crude oil recovered by spontaneous imbibition tests from the calcite cores. Results evidenced that, by using brine containing 2.9ppm×105ppm of total ion, it were obtained ORF values of 8.9% at 90°C temperature and atmospheric pressure, and 36% at 150°C temperature and 145psi pressure. Meanwhile with the inclusion of C12TAC at the same temperature and pressure conditions used in pure brine experiments, noticeable increased ORF values of 36% and 44%, respectively, were found. From the molecular interaction strengths between C12TAC and the fractions present in the oil, it has been evidenced also the oil disaggregation as well as the subsequent oil viscosity reduction, but finally without significant wettability alteration of the calcite core. A saturated, aromatics, resins and asphaltenes (SARA) component analysis revealed a significant change in composition moving from their original values of 20.6, 21.0, 35.5 and 22.9%, respectively, to 31.0, 23.2, 28.7 and 17.2%, accordingly. The lack of wettability alteration of C12TAC in such process is due to a weak interaction in C12TAC:Res and C12TAC:Asph molecular pairs followed by a clear diminishment of Res and Asph fractions in SARA, which reveals Asph and Res cannot be removed from rock surface. The quantum nature of the supramolecular assembling between the cationic surfactant and oil molecules is described by molecular orbitals analysis.