Background: Adjuvant aromatase inhibitors (AI) are standard of care for postmenopausal women with hormone receptor positive (HR+) early stage breast cancer but cause osteoporosis and fractures. ABCSG-18 showed previously that adjuvant denosumab significantly reduces clinical fractures (primary endpoint, HR = 0.5, p < 0.0001, Lancet 2015). Here, we present the impact of adjuvant denosumab on disease-free survival. Patients and Methods: 3,425 postmenopausal patients with early HR+ BC receiving adjuvant AI were recruited in 58 trial centers into this prospective, double-blind, placebo-controlled, phase-III trial. Patients were randomized 1:1 to receive either denosumab 60mg s.c. (N = 1712) or placebo (N = 1713) q6 months during AI therapy. We here present results of ABCSG-18’s secondary endpoint disease-free survival (DFS), including relevant subgroup and sensitivity analyses (accounting for cross-over either by censoring or by using a rank preserving structural failure time model). Results: After a median follow-up (FU) of 72 months, 287 events occurred in the placebo group, and 240 in the denosumab group. DFS was significantly improved in the denosumab arm (HR = 0.823, 95% CI 0.69-0.98, Cox p = 0.026*). In the denosumab group, DFS was 89.2% (95% CI 87.6-90.7) at 5 years and 80.6% (78.1-83.1) at 8 years of FU, compared to 87.3%, (85.7-89.0) at 5 years and 77.5% (74.8-80.2) at 8 years for patients who received placebo. Similar results were obtained from sensitivity analyses. No case of osteonecrosis of the jaw (ONJ) was recorded so far, despite proactive adjudication of potential cases by an independent expert panel. One potential atypical femur fracture was seen in the denosumab arm. Conclusion: Adjuvant denosumab improves disease-free survival of HR+ postmenopausal breast cancer patients receiving AI. Based on these results and the previously reported dramatic reduction of fractures, adjuvant denosumab 60mg s.c. q6 months should be offered to postmenopausal HR+ breast cancer patients receiving AI. * descriptive, without controlling for multiplicity. Clinical trial information: EudraCT #: 2005-005275-15.