Fulvestrant (Ful) is an effective and widely used agent for first- and second-line treatment of hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2-) metastatic breast cancer (MBC). However, there is no evidence of treatment after progression on Ful. Our study aimed to investigate the profile of daily practice regarding therapy after Ful. A consecutive series of 131 HR+, HER2- MBC patients who failed Ful 500 mg as first-line or second-line therapy from June 2014 to June 2017 in 6 institutions were included and analysed. Among 131 patients who failed Ful with similar baseline characteristics, 31 (23.7%) received endocrine therapy (ET), and 100 (76.3%) were treated with chemotherapy (CT). The most frequently applied CT regimen was capecitabine (32%), and the ET regimen was exemestane + everolimus (35.5%). Multivariate analysis showed that patients with bone-only metastasis were associated with lower CT use (OR = 7.97, 95% CI 1.51-41.84, P = 0.01). Among patients who received CT and ET as subsequent treatments, the median progression-free survival (PFS) was 7.5 months (95% CI 6.2-8.8) and 6.0 months (95% CI 4.1-7.9), respectively (p = 0.03). Among patients who were resistant to Ful (PFS < 6 months), the PFS on CT was significantly longer than that on ET (7.1 months vs 3.9 months, p = 0.024, HR = 0.5, 95% CI 0.26-0.97); however, among patients with a PFS ≥6 months on Ful, the efficacy of CT and ET was similar. Additionally, among patients with an older age, bone-only metastasis and ≥3 metastatic sites, no significant difference was observed between the CT and ET groups. Moreover, ET was much more tolerated than CT in terms of the incidence of grade 3/4 toxicities (9.6% vs 27%, P < 0.05). Median overall survival (OS) was not reached. Thus, our findings reveal the pattern of post-Ful treatment in current clinical practice and provide evidence on the efficacy, safety and choice of these treatments.