Purpose <p>Neoadjuvant immunotherapy in stage III melanoma has recently been shown to improve event-free and distant metastasis-free survival compared to adjuvant therapy. Pathologic response allows for subsequent personalization of surgery and omission/application of adjuvant therapy. We addressed the question whether neoadjuvant therapy allows an earlier and more to a more extent return to work in this curatively treated patient population.</p> Methods <p>In this single-center retrospective analysis of patients participating at the Netherlands, we interviewed via the telephone 88 stage III melanoma patients treated with neoadjuvant versus adjuvant immunotherapy in regards of their stopping work during therapy, and when returning partially or fully to work.</p> Results <p>Six, 12, and 24&#xa0;months post start of therapy at least partially worked 80% versus 61%, 84% versus 73%, and 91% versus 82% in the neoadjuvant versus adjuvant groups. Full return to work was observed at 6&#xa0;months in 52% versus 48%, at 1&#xa0;year in 71% versus 52%, and at 2&#xa0;years 82% versus 62%, respectively. Return to work (RTW) started in general in both groups after finishing the systemic therapies.</p> Conclusions <p>Our data suggest that the manner of therapy (neoadjuvant versus adjuvant) and potentially its treatment duration might be major factors influencing the timing and extent of RTW.</p> Implications for Cancer Survivors <p>A faster and full RTW is not only of importance for the patient’s well-being and QoL, but has also a significant financial impact on patients and their families.</p>