Abstract Background According to international guidelines, endocrine therapy (ET) is the preferred option for hormone receptor-positive (HR+) HER2-negative (HER2−) metastatic breast cancer. In spite of clear recommendations, these are not strictly followed in daily practice. The objectives of this study were to investigate the effect of the first anti-metastatic treatment therapy choice on progression-free survival (PFS) and overall survival (OS). Methods In this population-based study, we included patients with HR+/HER2− metastatic breast cancer recorded in the Côte d’Or Breast Cancer Registry. Differences in PFS and OS between patients initially treated with chemotherapy (CT) or ET were analysed in Cox proportional hazards models. In a sensitivity analysis, we used a propensity score (PS) to limit the indication bias. Results Altogether, 557 cases were included, 280 received initial ET and 277 received initial CT. PFS and OS in patients initially treated with ET was improved significantly when compared to patients with initial CT (respectively, HR = 0.83 (95% CI 0.69–0.99) and HR = 0.71 (95% CI 0.58–0.86)). The results of the sensitivity analysis supported these findings. Conclusion This study shows that treating patients with HR+/HER2− metastatic breast cancer with initial ET could provide a survival advantage in comparison with initial CT.