Objective To assess the safety and clinical efficacy of high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonists (GnRH-a), hysteroscopic surgery (hysteroscopic resection of adenomyosis and endometrial ablation) and levonorgestrel intrauterine system (LNG-IUS) for the treatment of adenomyosis patients with an unsatisfactory HIFU ablation. Design A retrospective analysis. Setting A specialized hospital in China. Population In all, 25 adenomyosis patients with HIFU ablation, the the non-perfused volume (NPV) ratio<50%, without fertility requirement. Methods All patients underwent HIFU ablation combined with GnRH-a, hysteroscopic surgery and LNG-IUS treatment (HGHL), with a follow-up period of at least 12 months. Main outcome measures The changes in dysmenorrhea and menstrual volume before, and at 3, 6 and 12 months following HGHL treatment. Results All 25 patients enrolled in the study were successfully treated with the HGHL combination with a median follow-up length of 15 months (range, 12–30 months). Mean value of the NPV ratio calculated immediately after the HIFU treatment was (32.8±10.4)%. Mean operation time, median intraoperative blood loss and median length of hospital stay of hysteroscopic surgery were 42.9±12.8 min, 10 (5,15) ml, and 3 (3,3) days, respectively. No significant complications were observed during HGHL treatment. Compared with the symptom scores before the HIFU treatment, the score of dysmenorrhea and menstrual volume decreased significantly at 3, 6 and 12 months after HGHL treatment ( p< 0.05), and no significant difference was observed between 3, 6 and 12 months after HGHL treatment ( p> 0.05). No recurrence was observed during the follow-up. Conclusions HGHL is a novel and effective combination therapy for adenomyosis with unsatisfactory HIFU ablation with the goal of preserving as much of the uterus as possible.