The relevant therapeutic outcomes obtained with the use of proton pump inhibitors for the treatment of gastric conditions have an important reflection on the prescribing habits of clinicians of primary and secondary care organizations. With the attempt to reduce their financial impact on the health systems, generic medications, obtained both from tradition distribution chain and from parallel import, have represented the main type of proton pump inhibitors used in clinics recently. The effect of parallel import and the use of the internet as an international distribution network significantly facilitates the entry of falsified medicines in the official channels of distribution. Since the interchangeability of different omeprazole preparations has been previously questioned, in this study we used Raman and 1H-NMR to characterise different omeprazole and esomeprazole formulations produced by different manufacturers and obtained from both traditional pharmacies and from unlicensed internet market in order to establish if any differences could be found to substantiate any different clinical performances. A chemometric study of Raman spectra allowed partial separation indicating that there are not sufficient chemical differences for PCA groups to be established using this analytical approach and for these specific medications. On the contrary, NMR investigations allowed the identification of impurities in internet samples, not detected by the Raman analyses, making this technique a valid candidate analytical tool to adopt for the investigation of falsified medicines.