The aim of this study was to evaluate the country-specific reporting status profile of immunomodulatory drugs (IMiDs)-related adverse events (ImrAEs) in real-world clinical practice, using data from the Japanese Adverse Drug Event Report (JADER) and Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) databases. Immunomodulatory drugs, including thalidomide and its derivatives, are a new class of anticancer and anti-inflammatory drugs. IMiD risk management programs have instituted sufficient measures to prevent fetal effects but do not address adverse effects experienced by patients themselves. To date, no study has compared ImrAE profiles across countries. Adverse events were defined using the preferred terms in the Medical Dictionary for Regulatory Activities. The number of reported adverse events related to IMiDs in each country (the United States and Japan) was investigated. In both Japan and the United States, myelosuppression, pneumonia, and neuropathy peripheral have been reported as adverse events suspected to be associated with IMiDs. Adverse event profiles differed between the countries. The number of adverse event reports for thalidomide increased transiently in the United States in 2008 following the multiple myeloma indication, and then exhibited a downward trend. The number of adverse event reports for lenalidomide and pomalidomide has increased in the United States since their launch. The number of transient reports increased in Japan in 2015, when pomalidomide was launched. In this study, the profile of ImrAEs was revealed using the FAERS and JADER databases. Our comparative safety study indicated the importance of comparing the safety profiles of IMiDs using post-marketing real-world data. It is important to focus on the adverse events experienced by patients taking IMiDs, as well as the effects of IMiDs on fetuses.