Objective To evaluate the clinical efficacy and safety of letrozole combined with gonadotropin (Gn) overlap protocol in ovulation induction for infertile patients with polycystic ovary syndrome (PCOS). Methods A retrospective analysis was conducted on 86 infertile PCOS patients treated from January 2024 to October 2025. Patients were divided into control group receiving letrozole alone (n＝42) and observation group receiving letrozole plus Gn (n＝44). Ovarian response parameters, ovulation and pregnancy outcomes, safety indicators, and endocrine changes were compared between the two groups. Results The observation group required fewer stimulation days (P＜0.05), while demonstrating a greater number of dominant follicles and thicker endometrium (all P＜0.05). The ovulation rate was higher than that in the control group (P＜0.05), and the clinical pregnancy rate also tended to be higher, although the difference was not statistically significant (P＞0.05). There was no significant difference in the incidence of ovarian hyperstimulation syndrome (OHSS) between the two groups (P＞0.05). Post-treatment luteinizing hormone (LH) and testosterone levels decreased more markedly in the observation group (all P＜0.05). Conclusion The letrozole combined with Gn overlap protocol improves ovarian response and ovulation rate with acceptable safety. It represents an effective ovulation induction strategy for infertile women with PCOS.