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Polypropylene (PP) is traditionally used in the production of medical devices, such as catheters, dialyzers, syringes due to its good chemical and thermal resistance, biocompatibility, and low cost. Sterilization can however damage these devices, when the polymer additive releases into physiological fluids, thereby harming the patient health. This article proposes to deposit biocompatible a?C:H:SiOx coatings onto PP surfaces and studies the coating stability after chemical sterilization. Five different chemical sterilizers, namely, hydrogen peroxide, ethanol, miramistin, formaldehyde, and ethylene oxide are used to compare their effect on the coating stability on the PP substrate. Untreated and sterilized samples are incubated in a liquid synthetic nutrient to obtain extracts that are used for sterility testing and determining the degree of interaction of samples with the nutrient medium. The changes in the coating functional groups and surface morphology are examined by using the Fourier transform infrared spectroscopy and the scanning electron microscopy, respectively. It is shown that the a?C:H:SiOx coating has a protective effect on the PP substrates subjected to chemical sterilization. The experiment results clearly showed that the ethanol sterilization causes the most serious changes in the structure of PP, and also leads to the barrier coating failure. On the other hand, ethylene oxide sterilization has a minimal effect on the structure of both uncoated and coated PP substrates.