Objective: To evaluate the safety and efficacy of using highly compressible calibrated microspheres in uterine artery embolization (UAE) for the treatment of uterine fibroids. Materials and Methods: This was a prospective multicenter study. Thirty-two women with symptomatic uterine fibroids were selected for UAE between January 2019 and March 2020. The participants completed the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire, underwent contrast-enhanced pelvic magnetic resonance imaging (MRI), and were submitted to anti-Müllerian hormone measurement, subsequently undergoing UAE with Embosoft microspheres. After six months, the patients again completed the UFS-QOL questionnaire and underwent pelvic MRI. Results: The most common symptoms were abnormal uterine bleeding (in 81.3% of the cases), pelvic pain (in 81.3%), and compression (in 46.9%). Of the 32 patients evaluated, 12 (37.5%) had anemia due to abnormal uterine bleeding. Thirty patients completed the study. Among those patients, we observed median reductions of 21.4% in uterine volume and 15.9% in dominant fibroid volume. We identified no adverse events that could be attributed to the material itself, although there were events attributed to the UAE procedure in general. Conclusion: For the treatment of uterine fibroids, UAE using Embosoft microspheres shows satisfactory results, providing reductions in uterine and dominant fibroid volumes, with a low rate of adverse events, and improving patient quality of life, as well as demonstrating safety and efficacy.