The aim of this study was to compare the effects of a 12-week course and four repeated 12-week courses of daily 5 mg ulipristal acetate (UPA) on reducing the volume and relieving symptoms of uterine fibroids. From 2016 to 2019, 287 female patients with uterine fibroids diagnosed using ultrasonography were recruited. The patients received four 12-week course treatments of daily UPA administration in the first and fourth sessions, respectively. During the first and fourth courses of UPA, we measured the volume of the fibroids using ultrasonography to study the effect on volume reduction. The measured outcomes included symptomatic relief and adverse effects. After the first UPA treatment course, menorrhagia was improved in 82.2% of patients. A total of 59.5% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 160.9 cm3 to 104.6 cm3. After the fourth treatment course, 87.4% of patients reported decreased bleeding. A total of 67.2% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 171.7 cm3 to 106.5 cm3. In 64 (38.1%) patients in group A and 36 (30.3%) in group B, the fibroid volume increased. Among them, 72% of patients showed improved symptoms. Uterine bleeding, pain, and reduced fibroid volume were adequately regulated in patients with symptomatic fibroids with four repeated 12-week courses of daily UPA.