Objective: Patients with metastatic breast cancer (MBC) with a history of treatment with anthracyclines and taxanes exhibit improvement with ixabepilone, a semi-synthetic analog of epothilone B. The present study, therefore, aimed to evaluate the safety and effectiveness of ixabepilone in patients with MBC who have previously received multiple lines of treatment Material and Methods: Patients with MBC who were treated with ixabepilone were included in the present study, which was designed as a retrospective multicenter analysis. Radiological responses were evaluated based on the RECIST criteria, and overall survival (OS) and progression-free survival (PFS) were calculated. The Common Terminology Criteria for Adverse Events version 5.0 was adopted to evaluate adverse events. Results: The analysis of 34 patients revealed a median OS of 10.0 months, a median PFS of 4.2 months, and an objective response rate (ORR) of 28%.The patients treated with ixabepilone prior to the fifth line of treatment exhibited a significantly better response (ORR 50%). In the subgroup analysis based on receptor status, ER+ and human epidermal growth factor receptor-2 (HER2+) patients presented the longest median PFS of 6.2 months. Conclusion: Ixabepilone demonstrated effectiveness in patients with MBC who had received multiple lines of treatments previously. The results suggest that early treatment regimens or targeted therapy for HER2+ patients could lead to better therapeutic outcomes when ixabepilone is administered. Ixabepilone is, therefore, a viable option for MBC patients who have received extensive treatment previously while maintaining a good performance status.