Objective ·To compare the pregnancy outcomes of infertile women with bilateral severe hydrosalpinx receiving neosalpingostomy or salpingectomy. Methods ·The single-center prospective cohort study from 2005 to 2012 focused on pregnancy outcomes of infertile women aged 20?40 years, with bilateral severe hydrosalpinx, undergoing bilateral neosalpingostomy or salpingectomy in International Peace Maternal and Child Health Hospital, Shanghai Jiao Tong University School of Medicine. The choice for treatment was based on a shared decision approach, and the participants were divided into the neosalpingostomy group and salpingectomy group. After registration of baseline characteristics, including age, birth place, reproductive history, preoperative hysterosalpingography results, surgical findings, and pregnancy outcomes, women were followed up on an annual basis until July 2020 for the occurrence of live birth by outpatient follow-up or telephone questionnaire. Intention-to-treat analysis and per-protocol analysis were applied to compare the pregnancy outcomes. Kaplan-Meier analysis and COX proportional hazard model were used to analyze the reproductive outcomes. In addition, subgroup analysis was performed based on age stratification. The main outcome measures were live birth rate, cumulative live birth rate, and factors affecting live birth. Secondary outcome measures included the mode of conception, time to live birth, biochemical pregnancy rate, clinical miscarriage rate, and ectopic pregnancy rate. Results ·A total of 113 women were included in the analysis, 58 women underwent bilateral neosalpingostomy, and 55 women underwent bilateral salpingectomy. The study demonstrated that in infertile women with bilateral severe hydrosalpinx, bilateral salpingectomy achieved higher cumulative live birth rate than bilateral neosalpingostomy (76.36% vs 62.07, HR=2.18,95%CI 1.37?3.45). In the neosalpingostomy group, 34.48% (20/58) live births were obtained after in vitro fertilization treatment, and 27.59% (16/58) live births were obtained through spontaneous conception which mainly occurred within 3 years after initial neosalpingostomy, while all live births in the salpingectomy group were obtained after assisted reproductive therapy. However, the risk of ectopic pregnancy was higher in the neosalpingostomy group than that in the salpingectomy group (20.69% vs 1.82%, P<0.001). No statistically significant differences regarding biochemical pregnancy and clinical miscarriage between the two groups were found. During the subgroup analysis, the cumulative live birth rate of the salpingectomy group (n=51) was significantly higher than that of the neosalpingostomy group (n=48) in women younger than 35 years old (HR=2.25, 95%CI 1.39?3.66), while between two groups of women aged 35 years old or older, there was no statistically significant difference in the cumulative live birth rate (HR=1.60, 95%CI 0.36?7.19). In addition, after adjustment for confounding factors including age, previous abortion history, fibroid, benign ovarian cyst, and endometriosis, COX proportional hazard analysis revealed that salpingectomy was positively correlated to live birth compared with neosalpingostomy (aHR=1.94, 95%CI 1.18?3.18). Conclusion ·For infertile women with bilateral severe hydrosalpinx, neosalpingostomy provides the possibility for spontaneous conception but also brings about certain risk of ectopic pregnancy. Bilateral salpingectomy can achieve higher cumulative live birth rate while receiving postoperative in vitro fertilization treatment.