OBJECTIVE: To determine the optimal lead follicle size for hCG trigger in letrozole intrauterine insemination (IUI) cycles, focusing on pregnancy outcomes. DESIGN: Retrospective cohort study. SUBJECTS: 724 letrozole-IUI cycles conducted at Omega Fertility Clinic between January 1, 2018, and September 30, 2023. EXPOSURE: Patients received letrozole for ovulation induction from cycle days 3-7, with follicle development monitored via transvaginal ultrasound. hCG was administered when a lead follicle reached the desired size, followed by IUI. MAIN OUTCOME MEASURES: The primary outcome was clinical pregnancy rate. Lead follicle sizes were categorized (≤18 mm, 19-23 mm, ≥24 mm) and dichotomized using thresholds from the ROC curve and Youden's index. RESULTS: Among 724 cycles, 92 resulted in clinical pregnancy. Clinical pregnancy rates were 8.45% for follicles ≤17 mm, 8.89% for 18 mm, and increased from 12.92% (19 mm) to 18.52% (22 mm) before declining to 11.43% for follicles ≥24 mm. Biochemical pregnancy rates followed a similar trend. Logistic regression revealed significantly higher odds of clinical pregnancy for follicles 19-23 mm (adjusted OR = 1.71, 95% CI: 1.01-3.03) compared to ≤18 mm. Follicles ≥24 mm had an adjusted OR of 1.80 (95% CI: 0.98-3.31), narrowly crossing the null, suggesting a possible effect despite not reaching statistical significance. The optimal threshold for follicle size was 19 mm, based on ROC curve analysis. Dichotomized analysis confirmed higher odds of clinical pregnancy for follicles ≥19 mm (adjusted OR = 1.74, 95% CI: 1.01-3.01). CONCLUSION: The optimal lead follicle size for hCG trigger in letrozole-IUI cycles is 19-23 mm, significantly improving clinical pregnancy rates. Follicles ≥24 mm may also yield positive outcomes and warrant further investigation. These findings provide evidence-based guidance for optimizing letrozole-IUI treatments.