Abstract: Objective To evaluate the efficacy and safety of fulvestrant (FUL) in multi-line endocrine therapy on hormone receptor (HR) positive metastatic breast cancer. Methods A total of 60 patients with HR positive metastatic breast cancer were treated with fulvestrant in our hospital from June 2010 to December 2013.Their clinical data, the efficacy of FUL, influencing factors and safety were retrospectively analyzed. Results Of the 60 patients with median age of 54.5 years, 23 cases were in stage Ⅰ/Ⅱ, 18 cases were in stage Ⅱ/Ⅳ, 47 cases received adjuvant endocrine therapy, and 50 cases received chemotherapy after recurrence. The ORR and CBR after FUL treatment (≥ 24 weeks) was 6.7%, 30.0%, respectively, and the median TTP was 4.6 months with median OS of 30.1 months. Twenty-nine out of 60 cases with both tmoxifen and aromatase inhibitor resistance achieved ORR of 6.9% and CBR (≥ 24 weeks) of 13.8% with median TTP of 4.0 months and median OS of 19.3 months. The efficacy of FUL was related to DFS, previous endocrine therapy and chemotherapy, and the dose of FUL. The main adverse events were injection site reaction, headache, gastrointestinal disturbance, weakness and hot flush. Most adverse events were moderate and reversible. Conclusion Fulvestrant is safe and effective in treatment of hormone receptor positive metastatic breast cancer.