Background: Eribulin mesylate (eribulin) is a microtubule inhibitor and a synthetic analog of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin was approved based on the randomized Phase 3 EMBRACE clinical trial, which showed an improvement in survival compared to chemotherapy (CT) of the physician's choice. The efficacy and safety of eribulin treatment in real-world settings has been reported in several studies: Korean and Chinese multicenter retrospective studies and a meta-analysis from 2020. Methods: We included all patients treated with eribulin between January 24, 2013 and September 14, 2022 at the Institute of Oncology Ljubljana (85.4% of patients) and University Medical Centre Maribor (14.6%). Clinical data were collected retrospectively from paper and electronic patient records. The primary endpoints were median progression-free survival (PFS), overall survival (OS), response rates and safety. We performed a descriptive statistical analysis and a survival analysis using the Kaplan-Meier method. Results: 205 patients, whose average age was 58.6 (29-88) years, were included in the study. The majority (79%) had a hormone receptor (HR+) positive tumor, 12.2% were HER2 positive and 16.6% were triple negative. 32/205 (15.6%) were primary metastatic. Of the remaining 173 patients, 160/173 (92.4%) received adjuvant therapy, of which 15% received hormone therapy, 23.1% received CT and 61.9% received both. At the start of treatment with eribulin, 84.9% had visceral tumors and 14.6% had tumors in the CNS. The median number of all treatment lines was 6 (range 2–15) and the median number of CT lines was 4 (0–13). The ECOG performance status was: 0 in 4.9%, 1 in 53.2%, 2 in 35.1% and 3 in 4.9% and 4 in 0.5% of patients. The objective response rate was 7.3% and clinical benefit was achieved in 27.3%. The median CT line in which eribulin was used was the fourth (1–10). Eribulin was used as the last CT line in half of the patients. The median PFS was 3.01 months (95% confidence interval 2.56–3.47) and the median OS was 6.68 months (95% confidence interval 5.60–7.77). Patients who received eribulin in the first 3 lines of treatment had a better OS than those who received eribulin in later lines. Adverse events (AEs) occurred in 52.7%. Eribulin therapy was discontinued due to AEs in 18.5% of patients. The most common AE was fatigue (25.9%), followed by neuropathy and neutropenia (22.9% and 18%). Conclusions: In our retrospective analysis, we found significantly worse results of treatment with eribulin than in previous studies. In our population, eribulin was used in the late stages of treatment and in older patients with poorer performance status. The proportion of patients with visceral and CNS tumors was higher. The side effects were comparable.