OBJECTIVE: To evaluate the impact of changes in perceived workplace support (PWS) and overall lifestyle on depression and burnout amongst UK-based healthcare professionals (HCPs) over 3-years, and the impact on staff attrition. METHODS: Online surveys at baseline (July-September,2020), 4-month, and 3-year follow-up, assessing depression (PHQ-9), burnout domains, PWS and lifestyle. The 3-year follow-up assessed intention-to-leave role. RESULTS: Over four-months (n = 614), improved lifestyle and PWS were associated with reduced depression, and PWS was associated with reduced depersonalisation. Over three-years (n = 309), improved lifestyle was associated with reduced depression and emotional exhaustion, and improved PWS was associated with reduced emotional exhaustion and depersonalisation. A unit increase in PHQ-9 score was associated with 10% increased risk of intention-to-leave within next 2-years. CONCLUSIONS: There is an important role of organisational-based approaches to mitigate both depressive symptoms and burnout in HCPs, with subsequent potential benefit of reduced attrition rate.