Background: State-of-the-art adjuvant endocrine therapy with aromatase inhibitors (AI) compromises bone health in postmenopausal patients with hormone receptor-positive (HR+) breast cancer, increasing fracture incidence. Adjuvant treatment with the anti-RANK ligand denosumab (Dmab) counteracts these side effects and may improve outcomes. We here report the final long-term outcomes of the ABCSG-18 trial (ClinicalTrials.gov NCT00556374). Methods: In this prospective, double-blind, placebo-controlled, phase 3 trial, 3,425 postmenopausal patients with early HR+ breast cancer on AI therapy were randomised in 58 trial centers between 2006 and 2013 to receive either Dmab 60 mg or placebo s.c. every 6 months (q6m). The primary endpoint was time to first clinical fracture, secondary disease outcome-related endpoints were disease-free survival (DFS), bone-metastasis free survival (BMFS), and overall survival (OS). In addition to the main endpoint analyses reported previously, exploratory long-term follow-up was conducted in ABCSG-18. Main time-to-event analyses were based on stratified Cox models. Sensitivity analyses accounting for treatment cross-over associated with a late Dmab open-label phase, as well as for receiving any anti-resorptive agents were performed. Results: For this final protocol-defined analysis, median follow-up is 8 years (Q1,3: 6, 9.6), and all patients had ended their randomly assigned double-blind treatment (Dmab 60mg s.c. q6m n = 1711; placebo s.c. q6m n = 1709) for a median of 5 years. DFS was improved in the Dmab group versus the placebo group (309 versus 368 DFS events, hazard ratio (HR) 0.83, 95% CI 0.71-0.97, p = 0.016), resulting in an absolute 9-year DFS difference of 3.5% (79.4% vs 75.9%, respectively). When censoring for late cross-over and use of anti-resorptive agents, the DFS difference was confirmed (HR 0.82, p = 0.010). BMFS was improved by 19 per cent (HR 0.81, 95% CI 0.65-1.00, p = 0.047) in the Dmab group, and OS was improved by 20 per cent in the uncensored analysis (127 versus 158 OS events, HR 0.80, 95% CI 0.64-1.01, p = 0.065), and 26 per cent after censoring (HR 0.74, 95% CI 0.58-0.94, p = 0.013). The previously reported marked reduction in clinical fractures persisted even long-term, with 201 fractures in the Dmab and 255 fractures in the placebo group (HR 0.76, 95% CI 0.63-0.92, p = 0.004). No new toxicities for this (low) bone-protective dose of adjuvant Dmab were reported, particularly no ONJ occured.. Conclusions: Adjuvant Dmab 60mg every 6 months during AI therapy is safe, and markedly reduces treatment-induced clinical fractures even in the long-term. DFS, BMFS, and OS are improved in this descriptive final long-term analysis of ABCSG-18. Adjuvant denosumab should be considered for routine clinical use in postmenopausal patients with HR+ breast cancer. Clinical trial information: NCT00556374.