Antibiotics are often only available in predefined pack sizes, which may not align with guideline recommendations. This can result in leftover pills, leading to inappropriate self-medication or waste disposal, which can both foster the development of antibiotic resistance. The magnitude of inappropriate pack sizes is largely unknown. The objective of this study was to evaluate the potential non-conformity of prescribed antibiotic pack sizes. This retrospective observational study was based on claims data from a large Swiss health insurance company. The study analysed the prescriptions of eleven different antibiotic substances recommended for the five most common indications for antibiotics in Switzerland. All prescriptions for adult outpatients issued by general practitioners in 2022 were included and extrapolated to the entire Swiss population. Potential non-conformity was defined as a mismatch between the total dosage in a pack and the total dosage recommended. A total of n = 947,439 extrapolated prescriptions were analysed. In 10 of 23 of all analysed substance/indication combinations none of the prescribed packs aligned with the respective guideline recommendation. Considering pack sizes in which the total prescribed dosage of a substance did not correspond to any of the total dosages recommended in at least one of the guidelines, 31.6% of prescriptions were potentially non-conform and an estimated number of 2.7million tablets were overprescribed. We found a large discrepancy between prescribed pack sizes and guideline recommendations. Since inadequately prepacked antibiotics may lead to antibiotic resistance and unnecessary waste, efforts are needed to implement alternatives like exact pill dispensing.