Co-amorphous drug systems were recently introduced as potential drug delivery systems for poorly water soluble drugs in order to overcome problems associated with amorphous materials. The improved physical stability and dissolution of these systems was attributed to molecular interactions between the co-amorphous partners, such as hydrogen bonds. However, molecular level characterization with vibrational spectroscopy of even the amorphous drugs alone presents a significant challenge. This becomes even more complicated when more than one compound is present in the material under investigation. In this study, the co-amorphous drug mixture containing naproxen (NAP) and indomethacin (IND) was investigated using infrared spectroscopy (IR) and quantum mechanical calculations. The structures of both drugs were optimized as monomer, homodimer and heterodimer using density functional theory and used for the calculation of IR spectra. Conformational analysis confirmed that the optimized structures were suitable for the theoretical prediction of the spectra. Vibrational modes from the calculation could be matched with experimentally observed spectra for crystalline and amorphous NAP and IND, and it could be shown that both drugs exist as homodimers in their respective individual amorphous form. With the results from the experimental single amorphous drugs and theoretical homodimers, a detailed analysis of the experimental co-amorphous and theoretical heterodimer spectra was performed and evaluated. It is suggested that NAP and IND exist as heterodimers in the co-amorphous mixture when quench cooled together from the melt in a 1:1 molar ratio.