Objectives The aim of the current study is to gain insight into the factors that benefit vitality and resilience of healthcare workers during the COVID-19 pandemic, to develop and direct specific support strategies. Design, setting and participants This study applies a qualitative design, consisting of six focus groups and five interviews among 38 frontline healthcare workers in a large Dutch academic hospital. Included were professionals of the intensive care unit, COVID-19 departments, infection prevention units and facility management services. The study was conducted in October and November 2020, during the second wave of the COVID-19 pandemic. Data analysis Thematic analysis was applied to focus group and interview data to gain insight into the factors that contribute to maintaining vitality and resilience, and to assess specific support needs. Results Data analysis of the focus groups and individual interviews resulted in a thematic map of the factors that contribute to maintaining resilience and vitality. The map stretches over two axes: one ranging from a healthy basis to adequate professional functioning and the other from individual to organisation, resulting in four quadrants: recharge and recover (healthy basis, individual), safety and connectedness at work (healthy basis, organisational), collaboration (professional functioning, organisational) and professional identity (professional functioning, individual). Conclusion Areas for organisational support strategies to increase vitality and resilience among healthcare professionals are: consistent communication, realistic job performance expectations, monitor and improve mental resilience, showing appreciation and act upon practical support requests.