OBJECTIVES: To conduct a review of the orphan drug recommendations made by the European Medicines Agency (EMA) to date and to consider projections on potential future designations and likelihood of marketing authorisations. METHODS: All orphan drug recommendations made by the EMA were analysed according to designation date, therapeutic area as categorised by the British National Formulary (BNF) and type of recommendation. Statistical analyses were undertaken in R and included projections up to 10 years, Spearman’s rank correlation coefficients such as type of recommendation and therapeutic area, and significance testing. Trends and likelihood of future marketing authorisation were extrapolated from the available data. RESULTS: The first orphan drug designation was granted by the EMA in 2000. At the time of analysis (May 2016), a total of 1674 drugs had been assessed. 1344 drugs (80%) received a positive orphan drug designation, whereas only 21 (1%) received a negative recommendation, 295 (18%) were withdrawn and 14 (1%) applications expired. Overall, the number of orphan drug applications increased year-on-year, with applications reaching a peak of 150 in 2015. The most common therapeutic areas included malignant disease and immunosuppression, nutrition and blood and respiratory. A significant correlation was observed between a positive recommendation and drugs treating malignant disease and immunosuppression (Spearman’s rank correlation coefficient: 0.9382; p < 0.001). Projections on orphan drug designations, based on the current rate of positive recommendations, estimated that around 4,701 orphan drug designations could have been granted by 2026. CONCLUSIONS: The majority of applications for orphan designation are successful. Projections estimating increasing numbers of orphan drug designations and likelihood of marketing authorisation require consideration by reimbursement agencies across Europe. Ongoing work will explore the trends in withdrawal of orphan designation at the point of market authorisation.