Background <p>PCOS is a common endocrine gynecological disorder, and its associated hormonal abnormalities and ovulatory dysfunction are leading causes of infertility. Ovulation induction is considered a fundamental treatment for PCOS patients. Clomiphene and letrozole are currently widely used ovulation-inducing agents. This study employs meta-analysis to comprehensively and systematically evaluate the clinical efficacy and adverse effects of letrozole combined with clomiphene in the treatment of PCOS.</p> Objective <p>The aim of this study is to compare the clinical efficacy and adverse effects of letrozole combined with clomiphene in the treatment of PCOS, providing a theoretical basis for therapeutic decision-making.</p> Methods <p>RCTs on letrozole combined with clomiphene for PCOS were retrieved from databases including PubMed, EMBASE, Cochrane Library, CNKI, Wanfang Medical Network, VIP Chinese Journal Service Platform, and CBM, with the search period spanning from database inception to March 2025. Data analysis was performed using Review Manager 5.3 and Stata software. Dichotomous variables were analyzed using RR with 95% CI, while continuous variables were assessed using SMD with 95% CI. The Cochrane Risk of Bias tool was used to evaluate the bias and risk of eligible studies. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in included studies.</p> Results <p>A total of 10 studies involving 931 PCOS patients were included. Compared with the control group, letrozole combined with clomiphene significantly improved pregnancy rates (RR = 1.50, 95% CI: 1.228–1.77, <i>P</i> &lt; 0.00001), ovulation rates (RR = 1.29, 95% CI: 1.15–1.444, <i>P</i> &lt; 0.0001), and estradiol levels (SMD = -1.13, 95% CI: -2.02 to -0.24, <i>P</i> = 0.001). However, no significant effects were observed on luteinizing hormone levels (SMD = -0.48, 95% CI: -1.16 to 0.21, <i>P</i> = 0.17), follicle-stimulating hormone levels (SMD = -0.45, 95% CI: -1.08 to 0.17, <i>P</i> = 0.15), endometrial thickness (SMD = 0.69, 95% CI: -0.57 to 1.96, <i>P</i> = 0.28), number of mature follicles (SMD = 0.83, 95% CI: -0.26 to 1.93, <i>P</i> = 0.15), diameter of mature follicles (SMD = 0.77, 95% CI: -0.55 to 2.09, <i>P</i> = 0.25), miscarriage rates (RR = 0.38, 95% CI: 0.18 to 0.81, <i>P</i> &lt; 0.0001), or adverse effects (RR = 0.77, 95% CI: 0.23 to 2.64, <i>P</i> = 0.68).</p> Conclusion <p>Letrozole combined with clomiphene therapy helps improve ovulation rates, pregnancy rates, and hormonal levels in PCOS patients.</p>