Background. Depot GnRH analogs represent the treatment of choice for central precocious puberty (CPP). Few data are available on pubertal suppression for the newer 3-month formulations. In addition, comparison between the monthly and quarterly tripotorelin depot is lacking. Aim: To assess the efficacy on pituitary and gonadal suppression of triptorelin 11.25 mg/3 months in girls with CPP and to compare the new formulation with triptorelin 3.75 mg/28 days. Patients and Methods: Thirty-five girls with clinical and endocrine diagnosis of CPP (puberty onset <8 yr). All but three girls were White Italians (Indian n = 2; Hungarian, n = 1). The girls were admitted to treatment with triptorelin depot (IPSEN-Biotech, Milan, Italy) in quarterly (group A: n = 15) or monthly (group B: n = 20) formulation. Patients were re-evaluated after 3 and 6 months of therapy. Results: In both groups, peak LH values (IU/1) were significantly decreased (p <0.005) at 3 (group A 0.8 ± 0.4; group B 1.0 ± 0.4) and 6 months (group A 0.8 ± 0.4; group B 1.0 ± 0.3) in comparison with baseline values (group A 22.5 ± 16.1; group B 24.0 ± 16.7); no differences were found between peak LH values at 3 and 6 months. Baseline LH values (IU/I) also decreased (group A: 0 mo 1.9 ± 1.7, 3 mo 0.3 ± 0.2, 6 mo 0.3 ± 0.2; group B: 0 mo 2.2 ± 2.1, 3 mo 0.4 ± 0.3, 6 mo 0.4 ± 0.2) No LH peak levels above the threshold for complete suppression were detected in either group. Basal and peak FSH as well as basal 17β-estradiol concentrations also showed a significant decrease at 3 months in both groups and stabilized thereafter. There were no significant differences between the patients treated by the quarterly or monthly preparation. No side effects were recorded. Conclusion: Triptorelin 11.25 mg/3 months is able to suppress the LH peak to prepubertal values in 100% of examined patients at 3 and 6 months of therapy. In addition, the triptorelin 11.25 mg/3 months formulation was equally effective in suppressing pituitary and gonadal secretion as the 3.75 mg/28 days preparation, suggesting that the new formulation is as effective as the monthly formulation, and that it can be the initial treatment in girls with CPP.