ObjectiveThere have been rare data on letrozole for height improvement in girls. This study aimed to clarify the efficacy and safety of combination therapy with recombinant human growth hormone (rhGH), gonadotropin-releasing hormone analog (GnRHa), and letrozole in improving the height of girls with short stature and advanced bone age. MethodsThis was a hospital record–based retrospective study. Follow-up was conducted on girls with short stature who received treatment with rhGH, GnRHa, and letrozole at outpatient clinics in our hospital. The treatment group included a total of 29 participants. Before treatment, the mean age of the patients was 11.17 years, and the mean treatment duration was 17.31 months. The control group consisted of 29 short-statured girls who received rhGH/GnRHa treatment, with the mean age and treatment duration of 12.43 years and 16.59 months, respectively. ResultsThe predicted adult heights (PAHs) before and after treatment were 155.38 and 161.32 cm (P < .001). The ΔPAH in the treatment group was 4 cm higher than that in the control group (5.85 vs 1.82 cm, P < .001). Significant differences were noted in the height standard deviation scores of bone age (P < .001) and chronological age (P = .003) before and after treatment. There was an increasing body mass index during therapy (P = .039). The height gain was 8.71 ± 4.46 cm, and the growth rate was 6.78 ± 3.84 cm per year. ConclusionCombined treatment with GH, GnRHa, and letrozole can enhance the adult height and PAH in short-statured girls, and no significant side effects have been reported.