OBJECTIVES: In the last years HTA-Scientific-Advice (HTA-SA) has been assuming a relevant role in decision process for assessment of new technologies for pricing and reimbursement in Europe. Since the beginning of the SA-initiatives, AIFA has been involved in multi-dimensional and multi-national advices: parallel-SA with European Medicines Agency (EMA), European-Network of HTA (EUnetHTA) Early-Dialogue, Tapestry Networks, National HTA-SA. The AIFA-HTA-SA procedure relates the assessment of manufacturer’s briefing book; consultancies with clinical and HTA experts; face-to-face meeting with manufacturer and final report. This study aims at presenting  an analysis of the HTA-SA programs over the last 3 years. METHODS: Comparative analysis of issues evaluated in different types of HTA-SA has been conducted, in terms of clinical development program (patients’characteristics and selection; choice of comparator; trial design; choice of endpoints, including patient-reported-outcomes, stratification/subgroups; safety), cost-effectiveness (modeling, resource utilization, utility values) and Place in Therapy (value proposition, added benefit). Finally, an analysis of concordance between manufacturers proposal and AIFA-advice has been performed. RESULTS: From 2011 to 2013, a total of 21 HTA-SAs were performed: 3 Tapestry-Networks-SAs; 3 National-HTA-SAs; 7 EUnetHTA-Early-Dialogues; 8 parallel-EMA-HTA-SAs. Nervous system and cancer diseases were the main therapeutic areas of requests, accounting for 57% of total HTA-SAs (respectively 6 products for each). The majority (52,4%) of HTA-SAs were requested in an early stage of clinical development (Phase I-II). The comparative analysis showed that clinical development items were systematically analysed among different types of HTA-SA, while the domains of cost-effectiveness and place in therapy were more relevant for EUnetHTA Early Dialogues and National HTA-SAs. The concordance analysis showed that target population, stratification/subgroups and choice of comparator(s) were critical issues. CONCLUSIONS: The HTA-SA-activities respond to the emerging need of early interaction among manufacturers, regulators and HTAs. Different types of HTA-SA reflect different institutional bodies approaches and peculiarities. The National-HTA-SA-program is expected to increase in the next future.