ObjectiveTo identify, review and synthesise qualitative literature on healthcare professionals’ adaptations to changes and challenges resulting from the COVID-19 pandemic.DesignSystematic review with meta-synthesis.Data sourcesAcademic Search Elite, CINAHL, MEDLINE, PubMed, Science Direct and Scopus.Eligibility criteriaQualitative or mixed-methods studies published between 2019 and 2021 investigating healthcare professionals’ adaptations to changes and challenges resulting from the COVID-19 pandemic.Data extraction and synthesisData were extracted using a predesigned data extraction form that included details about publication (eg, authors, setting, participants, adaptations and outcomes). Data were analysed using thematic analysis.ResultsForty-seven studies were included. A range of adaptations crucial to maintaining healthcare delivery during the COVID-19 pandemic were found, including taking on new roles, conducting self and peer education and reorganising workspaces. Triggers for adaptations included unclear workflows, lack of guidelines, increased workload and transition to digital solutions. As challenges arose, many health professionals reported increased collaboration across wards, healthcare teams, hierarchies and healthcare services.ConclusionHealthcare professionals demonstrated significant adaptive capacity when faced with challenges imposed by the COVID-19 pandemic. Several adaptations were identified as beneficial for future organisational healthcare service changes, while others exposed weaknesses in healthcare system designs and capacity, leading to dysfunctional adaptations. Healthcare professionals’ experiences working during the COVID-19 pandemic present a unique opportunity to learn how healthcare systems rapidly respond to changes, and how resilient healthcare services can be built globally.