Background: Adjuvant treatments with PD-1 and BRAF+MEK inhibitors significantly prolong recurrence-free survival in stage III cutaneous melanoma. However, the effect on overall survival is still unclear. After the approval of adjuvant treatments with PD-1 inhibitors and BRAF+MEK inhibitors, based on recurrence-free survival data, these treatments have been widely implemented. However, there are significant side effects and costs of the treatment, and the overall survival effect remains a highly anticipated outcome. Methods: Clinical and histopathological parameters were obtained from the Swedish Melanoma Registry that covers nearly all (99%) primary cutaneous melanomas diagnosed. Information on deaths was received from the Cause of Death Registry, a virtually complete register of all deaths in Sweden. Patients diagnosed with stage III melanoma between 2016 and 2020 were included and divided depending on if they were diagnosed before or from July 2018, the timepoint when adjuvant treatment was introduced in Sweden (designated as pre- and post-cohorts). In Sweden, approved treatments are freely available for all residents and there is a high-adherence to national treatment guidelines. Data was retrieved for the age and sex of the patients, the site, histopathological subtype, Breslow thickness and ulceration of the primary melanoma, type of locoregional spread and numbers of affected lymph nodes. Patients were followed until the end of 2021. Melanoma-specific and overall survival were calculated using the Kaplan-Meier method and Cox regression analyses. Results: There were 1371 patients diagnosed with stage III melanoma in Sweden in 2016-2020. The median time of follow-up in the pre-cohort was 57 months (range 42-72 months) and in the post-cohort 27 months (range 12-42 months). The 2-year overall survival rates, comparing the 634 patients in the pre-cohort and the 737 in the post-cohort, were 84.3% (95% CI 81.4-87.3) and 86.1% (95% CI 83.4-89.0), respectively, with an adjusted HR 0.91 (95% CI 0.70-1.19, P= 0.51). Further, no significant overall or melanoma-specific survival differences were seen when comparing the pre- and the post-cohort in different subgroups depending on the age, sex or tumor characteristics. Conclusions: To our knowledge, this study is the first to assess the impact on overall survival from a national introduction of adjuvant treatment in stage III melanoma. In this nationwide, population and registry-based study, no survival benefit was detected in the cohort receiving adjuvant therapy. Considering also the significant side effects and costs, these findings encourage a careful assessment of the current recommendations on adjuvant treatment. To offer close follow-up, and only treat if relapse occurs, should be an option discussed with patients with fully resected stage III melanoma.