Aim: To determine the impact of educational materials (EMs) on the treatment compliance of postmenopausal women with hormone receptor-positive (HR+) early-stage breast cancer. Patients & methods: Patients (n = 2757) were randomized to standard aromatase inhibitors (AI) alone (group A) or with EMs (group B) in a global, real-world setting. Results: The 2-year results (n = 2242) showed EMs had no impact on compliance (82 vs 82%, group A vs B), compliance with initial AI (82 vs 81%) or persistence (90 vs 88%), confirming the 1-year interim analysis (n = 2567). Of the 2082 patients considered compliant at 1 year, 77% remained compliant at 2 years. Discontinuations (9%) were mainly attributed to AI-related side effects (68% of discontinuations). Exploratory analyses suggest a relationship between patient characteristics and compliance behaviors. Conclusion: EMs do not improve compliance in this patient population. Compliance and persistence are complex end points influenced by multiple variables. Side effects were the main reasons for discontinuations.