OBJECTIVES While there exist a number of incentives to stimulate research and development of orphan drugs (OD), the Health Technology Assessment (HTA) agencies do not offer specific path for OD in most countries where it is left to payer value judgement. This leads to a high inequity in patient access to OD. The study aims at comparing the HTA decisions, price and reimbursement level of OD in France and Italy. METHODS All OD assessed since 2000 were analysed. Prices, reimbursement rates and decision details were extracted for each drug using Farmadati Italia database for Italy and Transparency committee reports, AMELI’s national health insurance and Thériaque databases for France. RESULTS Among 74 OD approved in Europe 66 are available in Italy compared to 53 in France. All ODs available in France are officially available in Italy. The average delay between the market authorization and the price and reimbursement decision was about 16 and 17 months in France and Italy, respectively. In France all available drugs are 100% reimbursed through hospital, 36 molecules are available in retail pharmacy with reimbursement from 15% to 100%. In Italy only 9 molecules are reimbursed in retail pharmacy and other 10 are not reimbursed at all. In 63% cases ex-factory prices in Italy are higher than in France. The average price difference in price is 12 % with 50% of products sharing almost same price (less than 5% difference). No information is available in France on managed entry agreement, while it is publicly available in Italy. This prevents fair price comparison. CONCLUSIONS OD are more available in Italy, but reimbursement is poorer than in France. Prices are slightly higher in Italy but France displays multiple confidential rebates making it impossible to compare net prices. In Italy the actual accessibility depends a lot on regional level unlike France.