BACKGROUND: During the last two decades, health technology assessment (HTA) has become ubiquitous in the European Union (EU). Countries established HTA agencies to perform drug value assessment to inform payers and ensure drug prices are affordable. One of the tools used by HTA agencies and payers is the incremental cost-effectiveness ratio threshold considered as a proxy of budget limitation. Recent launch of European cross-border initiatives on drug procurement may indicate the failure of HTA alone to contain drug prices and budget impact. DISCUSSION: Drugs such as sofosbuvir, immunotherapies, and advanced therapies have elicited the gap between budget impact and cost effectiveness. It was realized that budget impact of efficient interventions could challenge sustainability of EU national health insurance due to the large number of affected patients. The National Health Service (NHS) in England introduced a budget impact provision that would delay access of drugs recommended by NICE for 3 years to control budget impact, unless the manufacturer consent to a substantial rebate for the initial 3 year-period. In an objective to contain pharmaceutical costs, about ten European cross-country collaborations for drug procurement have emerged since 2012, encompassing almost thirty countries. Although sharing multiple objectives, the ultimate goal of these initiatives is a joint procurement of expensive medicines, leveraging the population size of involved countries. This trend expresses the need for payers to complement HTA with procurement process. Payers are considering the negotiating power of joined countries as offering a wider market ensuring better price negotiations when following HTA process at country level. Joined procurements may also provide an opportunity for a differential pricing aligned on power purchase parity. CONCLUSION: Sofosbuvir case enlightens the gap between cost effectiveness and affordability. The emergence of multiple European cross-border initiatives on drug procurement may be a marker of HTA failure to support price setting.