Purpose <p>The COVID-19 pandemic posed substantial challenges to cancer care, raising concerns about the safety of ongoing endocrine therapy in women with breast cancer. However, real-world evidence on the association between endocrine therapy and COVID-19 outcomes in population-based cohorts remains limited.</p> Methods <p>A nationwide, register-based matched cohort study was conducted in Sweden, including women aged ≥ 55 years who received endocrine therapy for breast cancer during 2020. A total of 31,678 women were included: 8,879 treated with tamoxifen, 21,384 with aromatase inhibitors, and 1,415 with sequential therapy. Exposed women were matched 1:1 by age and region to population controls without breast cancer or estrogen-modulating therapy. Stage-stratified analyses were performed for early-stage and locally advanced breast cancer. Outcomes included COVID-19–related mortality (primary outcome), all-cause mortality, intensive care unit admission, COVID-19–related hospitalization, and laboratory-confirmed SARS-CoV-2 infection.</p> Results <p>COVID-19–related mortality did not differ between women receiving endocrine therapy and their matched population controls. Intensive care unit admission risk were comparable across groups. Tamoxifen was associated with lower all-cause mortality in early-stage breast cancer, whereas aromatase inhibitors were linked to higher all-cause mortality and increased COVID-19-related hospitalization in locally advanced disease. A modestly increased risk of SARS-CoV-2 infection was observed among tamoxifen users.</p> Conclusion <p>In this nationwide Swedish cohort, adjuvant endocrine therapy was not associated with increased COVID-19–specific mortality. These findings support the continued use of adjuvant endocrine therapy in women with breast cancer without added COVID-19 mortality risk and highlight stage-specific differences in outcomes, reinforcing the safety of endocrine therapy during pandemic conditions.</p>