Background <p>Endometriosis is currently considered a chronic disease for which long-term medical treatment is needed. The aim of this study was to evaluate the long-term efficacy and safety of dydrogesterone in Chinese women with endometriosis and dysmenorrhea in a real-world setting.</p> Methods <p>This was a retrospective study of endometriosis or dysmenorrhea patients who required conservative treatment and who were treated with 10&#xa0;mg oral dydrogesterone twice a day for 21 consecutive days for 12 consecutive cycles at Shaanxi Provincial People’s Hospital from May 2020 to October 2021. Changes in endometriotic lesion volume, dysmenorrhea, SF-36 score, menstrual status, and haemoglobin and Ca125 levels from baseline were measured. The volume change was calculated as follows: [(baseline lesion volume–lesion volume at follow-up)/baseline lesion volume]*100%. Changes &gt; 15%, ± 15%, and &gt;-15% were defined as lesions that were reduced, unchanged, and increased, respectively. Dysmenorrhea was assessed by means of visual analogue scale (VAS) scores. Wilcoxon signed-rank tests were performed to estimate the changes in the above aspects before and after treatment.</p> Results <p>This study included 48 patients with endometriosis or dysmenorrhea aged 25 to 47 years, and 38 patients completed 12 cycles of medication and follow-up. Forty-five patients had endometriotic lesions, among whom 38 (84.44%) had smaller or unchanged lesions and 7 (15.56%) had enlarged lesions. The endometriotic lesion volume changed from 65.73 ± 67.89 cm³ to 24.83 ± 21.60 cm³ (<i>p</i> &lt; 0.001). There was no significant difference in the initial lesion diameter among the reduced, enlarged, or unchanged groups (<i>p</i> = 0.082). The VAS score tended to decrease throughout the study (<i>p</i> &lt; 0.001). More than 80% (<i>n</i> = 37, 80.43%) of patients experienced relief of dysmenorrhea after 2 cycles of treatment, and more than 75% (<i>n</i> = 35, 76.09%) of patients stopped using analgesics after 3 cycles of treatment. Almost all patients showed significant improvements in their menstrual cycle regularity, quality of life scores, and haemoglobin levels during treatment (<i>p</i> &lt; 0.001). The incidence of adverse drug reactions was 32.69%, and all reactions were mild to moderate.</p> Conclusion <p>Dydrogesterone can effectively control endometriotic lesions in most women and significantly improve dysmenorrhea and quality of life.</p>