Background: Several health technology assessment (HTA) initiatives have been put in place in Europe: multi-HTA early advice (EUnetHTA), parallel scientific advice between European Medicines Agency (EMA) and HTA bodies, early dialogues between HTA bodies and EMA during adaptive pathways and priority medicines scheme and single national HTA early advice. Early HTA dialogues allow manufacturers to secure that their drug development plan addresses HTA agencies’ expectation but is not free of risk while benefits look obvious. Discussion: Before engaging in HTA early advice, pharmaceutical companies need to be well prepared to mitigate risk and get the most out of HTA bodies/EMA interactions. First, companies have to identify products for which to seek an advice and define portfolio priorities as process is time consuming. Then, companies have to identify appropriate timing to seek early HTA advice, i.e., very early in drug development or later. End of phase I might be too early while little information is available; HTA bodies might propose either unfocused or too much focused positioning. End of phase IIa might allow obtaining a better feedback when companies have actual questions on population/indication; on the other side HTA bodies could widely impact drug positioning and request substantial changes in drug development plan, while it will be more difficult at end of phase IIb, as phase III needs to be replicated in the phase II population to obtain license. Finally, advice category to be selected depends on expected alignments and potential influence between HTA agencies/ EMA which might complicate development plan. Single HTA advice may prove useful when manufacturer want to address country specific issues but may increase HTA bodies’ divergence in their requirements. Conclusion: Engaging in early dialogues with HTA bodies is product and company specific and requires careful benefit-risk assessment; this requires following standardised process to ensure enlightened decision.