Objective.A 3-month depot of leuprorelin acetate (LA) was introduced in China in July 2020. However, the clinical experience is limited. The purpose of this study was to compare the efficacy of a LA 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of central precocious puberty (CPP). Subjects and Methods. A prospective study, including 78 girls with CPP treated with LA, was conducted. 31 patients were treated with a LA 3-month depot, and 47 were treated with a LA 1-month depot. Participants were interviewed at baseline and 6 months. Anthropometric, metabolic, and reproductive data were assessed at each interview. Bone age, serum endocrine hormones, maximum diameter of uterus and volume of ovary of each patient were evaluated. A pharmacoeconomic evaluation was also conducted. Results. Treatment with a 3-month depot was similar to treatment with a 1-month depot in terms of baseline characteristics. After 6 months of treatment, a suppressed level of luteinizing hormone (LH) (LH < 2.5 IU/L) was found in 100% and 95% of the 11.25 mg and 3.75 mg groups, respectively. LH decreased from 2.11 +/- 1.83 and 2.82 +/- 2.31 at baseline (P=0.172) to 0.37 +/- 0.39 and 0.44 +/- 0.76 (P=0.758) in the 3-month and 1-month groups, respectively. Follicle stimulating hormone and estradiol levels, bone age/chronological age (BA/CA), height velocity, maximum diameter of uterus and volume of ovary did not show any distinction between the two groups after 6 months of treatment, but both were significantly ameliorated compared with the baseline. The loss of working time of parents and study time of patients and the numbers of visits, injections and laboratory examinations obviously decreased in the 3-month depots. Conclusion. An LA 3-month depot was equally effective and safe as a 1-month depot for hormonal suppression and bone maturation inhibition, providing clinical experience in China. The 11.25 mg depot of LA is a safe, efficient, and economical treatment method for the advanced activation of the hypothalamic-pituitary-gonadal (HPG) axis.