OBJECTIVES: To promote the research and development of drugs for rare diseases, like other countries, orphan designations have been granted to pharmaceuticals in Japan since 1993. We investigated the accessibility of orphan drugs in Japan by comparing the accessibility of orphan designated and marketing authorised drugs in the EU and the US. METHODS: The present study used the data available until the November 30, 2009 from the European Medicines Agency, US Food and Drug Administration and National Institute of Biomedical Innovation. The International Nonproprietary Names (INNs) were used for comparing authorised orphan designated drugs in Japan, the EU and the US. RESULTS: A total of 228 products had been granted orphan designation, of which 142 (62%) obtained marketing authorisation in Japan, which is equivalent to 122 in INNs. Meanwhile, the number of authorised orphan-designated medicines in INNs in the EU and the US was 57 and 198, respectively. Of the total 287 authorised orphan-designated pharmaceuticals in INNs in these 3 regions, 165 were inaccessible in Japan through the orphan designation system. Among such drugs, 25 (15%) were authorised orphan designated in both the EU and the US, 15 (9%) were authorised orphan designated in the EU alone and 125 (76%) were authorised orphan designated in the US alone. CONCLUSIONS: We observed that the orphan designation system in Japan has achieved certain results for increasing the accessibility of necessary drugs to patients suffering with rare diseases. However, several drugs are still not available in Japan, partly because of the difference in definitions of orphan disease among the 3 regions. To increase the accessibility to orphan drugs, further policy interventions should be considered.