Objective: To investigate the clinical efficacy and safety of laparoscopic focal resection combined with high-potency progesterone in the treatment of adenomyosis of uterus. Methods: 78 patients with adenomyosis who were treated in our hospital from January 2022 to December 2024 were selected as the study objects. According to random number table method, the patients were randomly divided into control group and observation group, with 39 cases in each group. The control group underwent laparoscopic resection. Observation group was treated with laparoscopic focal resection combined with dinorgestrel. The therapeutic effect, uterine volume, dysmenorrhea level [Visual analogue scale (VAS)], sex hormone level [Estradial (E2), Follicle-stimulating hormone, follicle-stimulating hormone (FSH), Luteinizing hormone (LH) levels] and adverse reactions during treatment between the two groups were analyzed and compared. Results: The total effective rate of observation group was significantly higher than that of control group (P<0.05). After treatment, the uterine volume and VAS scores of both groups were significantly lower than those before treatment, and the uterine volume and VAS scores of the observation group were significantly lower than those of the control group (P<0.05). After treatment, E2, FSH and LH levels in both groups were significantly lower than before treatment, and LH levels were significantly lower than control group. The levels of E2, FSH and LH in the observation group were significantly higher than those in the control group (P<0.05). There was no significant difference in the total incidence of adverse reactions between the two groups during treatment (P>0.05). Conclusion: Laparoscopic focus resection combined with dinorgestrel in the treatment of uterine adenomyosis can improve clinical efficacy, alleviate clinical symptoms, improve hormone levels, and have high safety.