To assess whether ulipristal acetate (UPA) improves adenomyosis-related heavy menstrual bleeding (HMB) persisting after the insertion of the levonorgestrel-releasing intrauterine device (Lng-IUD) and to evaluate the changes in the endometrium during treatment. This prospective study included patients with adenomyosis complaining persistence of HMB after at least 6 months from the insertion of the Lng-IUD. Adenomyosis was diagnosed by ultrasonography accordingly to the MUSA statement. Patients were offered a continuous treatment with UPA (5 mg/day; Gedeon Richter) for 6 months. The ultrasonographic characteristics of the endometrium were assessed before administering UPA, after 3 and 6 months of treatment. The endometrium was also evaluated by hysteroscopy after 3-month of treatment. At the end of treatment, patients rated the degree of satisfaction by using a Likert scale. The pictorial blood-loss assessment chart (PBAC) was used to estimate uterine bleeding. The intensity of pain symptoms was measured on a 100 mm visual analogue scale. 23 women were included in the study; the mean (±SD) length of use of the Lng-IUD prior to the administration of UPA was 9.0 (±2.2) months. 2 patients (8.7%) interrupted the double-drug treatment before the 6-month follow-up because of pain symptoms. At the end of the 6-month treatment, 73.9% of the patients (17/23) were satisfied or very satisfied. 81.0% of the patients (17/21) were amenorrheic; 4 patients had controlled uterine bleeding (PBAC 28-days score < 75). 5 patients (4.8%) reported worsening of pain symptoms. Endometrial thickness was similar at baseline and 6-month follow-up (p = 0.150). Most of the patients (76,2%; 16/21) had a homogeneous (IETA) endometrial patter at the completion of treatment. Hysteroscopy revealed hypotrophic endometrium in 87.0% of the patients (20/23); a chicken-wire vascular pattern was observed in 30.4% of the patients (7/23). The administration of UPA improves HMB persisting after the insertion of the Lng-IUD.