Quinidine is an active antimalarial compound extracted from the bark of Cinchona trees. The activity differences among structurally related molecules appears to depend on the absolute stereochemistry of some functional groups, a result that stimulated a detailed conformational analysis of these molecules of biological interest. In the present study, the potential energy surface (PES) for the antimalarial agent quinidine (C20H24O2N2) has been comprehensively investigated using the molecular mechanics (MM) and quantum mechanical semiempirical AM1 and PM3 methods. Six distinct minimum energy conformations were located on the multidimensional PES and also characterized as true minima through harmonic frequency analysis. The relative stabilities and thermodynamic properties are reported. The coexistence of different conformers is discussed for the first time in the literature based on the transition state (TS) structures located on the PES for the quinidine molecule. The theoretical results reported in the present study are in agreement with the experimental proposal, based on NMR data, that there are two conformations existing in solution for the quinidine molecule.