Background: Patient information leaflets (PILs) have proven to be a good source of information to prescribers, dispensers, and patients by providing important information about the proper use and handling of medicines. This study aimed to evaluate the conformance of the patient information leaflet of selected innovator and generic medicinal products to Ethiopian regulatory requirements. Method: A descriptive cross-sectional study design and stratified sampling technique were applied to collect product information leaflets from each pharmacological category of medicinal products. Result: Most of the PILs studied (96.4–99.6%) showed a high rate of conformance concerning nine parameters. However, the least percentage conformance (24.3–48.6%) was observed for the inclusion of product information regarding four parameters. Regulatory conformance of the innovator/comparator products in almost all of the parameters but clinical pharmacology of medicines was found to be higher than those of their generic counterparts. The European-manufactured medicines showed relatively higher conformance across parameters compared to Asian and African manufactured ones. Program drugs revealed better conformance than other classes of medicines in most parameters. Conclusion: The findings of this study indicated that, despite the efforts taken by the concerned body to establish a minimum regulatory framework to ensure the safety, quality, and efficacy of medicines, an indicative number of commercial packs of medicinal products in Ethiopia do not fulfill all the necessary information requirements set by the authority. Hence, the Ethiopian Food and Drug Authority (EFDA) should take maximum efforts to undertake intensive evaluation during pre-market authorization to ensure that commercial packs of medical products are accompanied by complete product information.