OBJECTIVES: Developing innovative treatments for rare diseases is intrinsically difficult due to small patient population sizes and the scarcity of high quality evidence. Orphan drug designation is attributed to drugs which have been developed to treat rare diseases; however, the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) define rare diseases differently. The objective of this study was therefore to investigate the number and type of orphan drug designations across the EMA and FDA. METHODS: Data on authorised drugs awarded orphan status by the EMA and FDA is freely available and was obtained from their respective websites. Authorised orphan drugs were analysed dating back to the first EMA orphan drug designation in 2002. RESULTS: The EMA designated 82 drugs orphan status, whilst the FDA designated 170 drugs orphan status. An upward trend in the number of drugs designated orphan status by the EMA was observed, whilst a downward trend was present in FDA orphan designations. The distribution of orphan drugs across WHO Anatomical Therapeutic Chemical (ATC) classifications appears to vary, for instance: 18% of EMA authorised orphan drugs were in the alimentary tract and metabolism group (ATC code A), compared to just 6% of FDA orphan drugs. Conversely, orphan drugs in the blood and blood forming organs category (ATC code B) comprised 2% of EMA authorised orphan drugs compared to 12% with the FDA. CONCLUSIONS: The EMA has designated half the number of drugs orphan status compared to the FDA however the number of authorised drugs designated orphan status appears to be on the rise in Europe. The pattern of orphan drugs across ATC groups appeared to differ between the EMA and FDA suggesting the regulatory bodies may have different preferences with regard to research and development in the various therapeutic fields.