Herein, the molecular structures of amide ↔ imide tautomers of articaine (ART) were computationally investigated at the DFT/B3LYP/6–311++G (d,p) methodology. Experimental FT-IR and UV-Vis characterisation results of ART were compared with the theoretical results of amide (ART-A) and imide (ART-I) forms. Thermodynamic parameters computed for each phase revealed that the amide tautomer of ART was preferred with energy values in the range of 11.9–13.8 kcal/mol. The modification in surface properties as a function of prototropic tautomerism in the ART molecule was studied by electrostatic surface properties (ESP) analysis. Frontier molecular orbital (FMO), natural bond orbital (NBO), and nonlinear optical (NLO) analyses were performed. It is revealed that energy gap values of the ART-I (4.670–4.738 eV) for each phase are slightly higher than those of the corresponding phases in the ART-A (4.515–4.586 eV). Therefore, it can be concluded that the imide form exhibits lower chemical reactivity compared to the amide form. Regarding NLO characteristics, dipole moment (μtot ), mean polarisability (αtot ), and mean first-order hyperpolarisability (βtot ) values of tautomers have been reported. It was determined that the βtot values computed for ART-A (0.653 × 10−30 esu) and ART-I (0.710 × 10−30 esu) were approximately twice the value of the standard urea.