: Illicit PDE-5 inhibitors are frequently encountered by regulatory agencies. Self-medicating with substandard and falsified (SF) PDE-5 inhibitors could be dangerous as they are likely taken without any medical supervision and might be of poor quality which could result in adverse reactions. In order to provide an overview of the quality deficiencies present in recently seized illicit PDE-5 samples that may pose health risks, we set out to identify the products’ different chemical and/or biological risks. Our results indicate that 38% of the samples harbored a chemical risk including the significant exceedance of the maximum recommended dosage, a large heterogeneity in API content between the different tablets in the same package or blister and the presence of only 40% of the claimed dosage. Moreover, our results also demonstrate that 16 of the 32 samples were not compliant with the internationally set microbiological quality standards. Startlingly, two samples were severely contaminated with potentially pathogenic bacteria, which could result in a gastrointestinal illness upon oral intake.