OBJECTIVES In Italy drug Health Technology Assessment (HTA) is conducted by the Scientific Technical Commission of Italian Medicines Agency (AIFA) with further negotiation between the manufacturers and the AIFA’s Pricing & Reimbursement Committee on price and reimbursement. After the decision is taken it is published in the official journal (Gazetta officale), the assessed drug is formally available for Italian patients next day. There does not exist a specific procedure for orphan drugs (OD), they are evaluated under the same conditions as drugs for common diseases. Pharmaco-economic studies are recommended for innovative drugs. The objective of the study is to review HTA decisions, prices and reimbursement of OD in Italy. METHODS All OD assessed in Italy since 2000 were identified. Prices, reimbursement rates and decision details were extracted for each drug using Farmadati Italia database. RESULTS Among 74 OD approved in Europe 66 molecules are officially available in Italy. It took 5-10 months from granting market authorization to final decision on pricing and reimbursement and publication in ‘Gazetta officale’. The mean time was about 17 months shorter than for common drugs. Only 9 of available molecules are fully reimbursed in Italy, reimbursement of 30 drugs is restricted to hospital use, 10 are not reimbursed and 5 are in a special class waiting a decision on reimbursement rate. For other drugs information is not available. Post-marketing surveillance studies were requested for a half of indications, AIFA registries were reported in 25% of cases. Annual treatment ex-factory price of OD varies from € 2 500 to almost € 1 000 000. CONCLUSIONS Almost 90% of approved OD are available in Italy. However, the actual situation often differs a lot from the official data as some drugs are unavailable from retail or hospital pharmacies. In addition, regional authorities contribute to inequity in access especially for “expensive drugs”.