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STUDY OBJECTIVE To study the effects of ulipristal acetate (UPA) on adenomyosis-associated clinical symptoms. DESIGN A retrospective, single-center observational study (Canadian Task Force classification II-2). SETTING A university tertiary referral center. PATIENTS Premenopausal women (163) with adenomyosis and symptomatic uterine myomas (41 patients, A + F group) versus a control group with only myomas (122 patients, F group) treated with the first course of UPA. INTERVENTIONS This was a retrospective study to assess the effects of a 12-week course of UPA (5 mg/d). MEASUREMENTS AND MAIN RESULTS Clinical symptoms including bleeding control, amenorrhea, pain outcomes, and self-perceived severity of the disease and quality of life. Amenorrhea was present in 90.4% of the A + F group compared with 77.6% in the F group (p = .0017). Optimal bleeding control was significantly higher in the adenomyosis group (pictorial blood loss assessment chart < 75) than in the F group (90.2% vs 73.8%, p = .028). At the end of the first UPA course, the self-reported visual analog scale scores in the A + F group were significantly higher than in the F group (p = .017), reflecting greater improvement in pain outcomes for women with adenomyosis. UPA treatment improved the quality of life in both study groups. Most of the women rated their global health status as "better" after the first UPA course than before the treatment (A + F group: 67.00% and F group: 80.50%, p = .223). CONCLUSION Treatment with UPA led to a significant reduction in the clinical symptoms of adenomyosis (bleeding and pain) and achieved a high rate of amenorrhea in a cohort of women with concomitant uterine myomas. Despite the limitations of the study, our results showed that UPA might be a good alternative treatment for adenomyosis.