Abstract Background To evaluate the acceptability of a risk-based breast cancer screening (BCS) strategy among professionals involved in MyPeBS study in 6 countries. Methods After qualitative interviews, a questionnaire was built with a Delphi method: to evaluate professionals’ basic understanding, satisfaction and reactions to each stage of the trial, opinions on BCS and its future. The questionnaire was distributed by emailing 698 investigators, who forwarded it to all categories of professionals involved in trial recruitment (physicians, medical secretaries, nurses, and mammography technicians). Descriptive statistics were used to summarize views on acceptability. Results Among the 198 respondents, most declared being at ease with the trial design and the concept of breast cancer risk estimation. They were mostly comfortable explaining the different trial steps, communicating risk estimation, and answering women’s questions. Some professionals were not comfortable explaining high (7.1%) and low-risk categories (9%) and did not feel sufficiently trained (26.5%). Although professionals were mostly confident about risk-based approaches and the potential of this to improve breast cancer screening (93.5%), 58% called for further validation of the risk-models to predict risk before implementation in population-based programs. They expressed concerns about the complexity of this screening strategy, stressing the need to properly inform the public and to train professionals in delivering risk assessment. Conclusion This first study assessing the perspectives of professionals delivering risk-based BCS. As professional acceptability is key for successful implementation, training for all professionals and tools to help them communicate risk to women will be necessary to develop risk assessment in BCS. Trial registration Study sponsor: Unicancer. My personalised breast screening (MyPeBS). Clinicaltrials.gov (2018) available at https://www.clinicaltrials.gov/ct2/show/NCT03672331 .