Generic formulations share the same active pharmaceutical ingredient (API), but differences in excipients can impact the quality and efficacy of formulations. In this study, four gastro-resistant pantoprazole tablet formulations were selected from the Serbian drug market to compare their dissolution profiles. The influence of high and low humidity on disintegration and dissolution was examined. The tablets were removed from the primary packaging and packed in plastic boxes, which were then placed in the desiccator with low (30%) and high (75%) humidity conditions for 1 week to simulate storing medicines in weekly pill organizers. Dissolution, disintegration, and uniformity of content were analyzed according to the 10 th European Pharmacopoeia. Pantoprazole content was determined using UV-Vis spectrophotometry. Dissolution profiles were compared with one-way analysis of variance and similarity factor analysis (f 2 ). Although a difference was detected in the dissolution profiles of pantoprazole tablets, the overall dissolution rate was satisfactory for all formulations in all conditions tested. After being exposed to high humidity, two formulations failed to meet the requirements for disintegration due to the enteric coating being damaged during the acid stage of the test. This could lead to the absence of therapeutic effect. Therefore, patients should be advised to keep their pantoprazole tablets away from high humidity, preferably in the original packaging.