Objective: To investigate the relationship between uterine niche and reproductive outcomes of in vitro fertilization (IVF) and intracy-toplasmic sperm injection (ICSI).Design: A retrospective cohort study.Setting: A reproductive medicine center.Patient(s): A total of 2,449 women with cesarean section history who underwent 2,874 IVF/ICSI cycles between January 2015 and December 2019. Intervention(s): A defect deeper than 2 mm visible under three-dimensional transvaginal sonography or hysteroscopy was defined as uterine niche. The IVF/ICSI outcomes of the first embryo transfer were obtained by telephone interview 1 year after embryo transfer regardless of fresh embryos or frozen-thawed embryos. Generalized estimating equations, logistic regression analyses, and propensity score matching were applied to clarify the relationship between uterine niche and IVF/ICSI outcomes.Main Outcome Measure(s): Primary outcome was live birth rate. Secondary outcomes were positive human chorionic gonadotropin test results, clinical pregnancy rate, implantation rate, miscarriage rate, and ectopic pregnancy rate.Results: After excluding 48 cycles for uterine malformation; 18 cycles for chromosome abnormality; 281 cycles for no available em-bryo or no embryo transfer; 5 cycles for oocyte donation; and 7 cycles for loss of follow-up, we finally included 2,231 women with 2,515 cycles in our study. Compared with women without niche, women with niche had reduced live birth rate (18.99% vs. 31.51%, : 0.51, 95% CI: 0.34-0.77), positive human chorionic gonadotropin test rate (34.08% vs. 46.40%, adjusted odds ratio [aOR]: 0.61, 95% confidence interval [CI]: 0.43-0.87), clinical pregnancy rate (29.05% vs. 42.25%, aOR: 0.57, 95% CI: 0.39-0.82) and implantation rate (25.87% vs. 36.95%, aOR: 0.53, 95% CI: 0.38-0.76). In all the sensitivity analyses, the niche group had a 7.28% to 18.22% increase in miscarriage rate even not all of them were statistically significant.Conclusion(s): Uterine niche may have a detrimental effect on subsequent fertility of women with cesarean section history undergoing IVF/ICSI treatment. Practitioners should be noted that women with uterine niches may be associated with adverse IVF/ICSI outcomes. (Fertil Steril (R) 2023;119:433-41. (c) 2023 by American Society for Reproductive Medicine.)