Background: Hysterectomy is commonly performed and may increase the risk of pelvic organ prolapse. Previous studies in parous women have shown an increased risk of pelvic organ prolapse surgery after hysterectomy. Parity is a strong risk factor for pelvic organ prolapse and may confuse the true relation between hysterectomy and pelvic organ prolapse. Objective: This study aimed to investigate whether hysterectomy performed for benign conditions other than pelvic organ prolapse leads to an increased risk of pelvic organ prolapse surgery in a cohort of nulliparous women. Study Design: We conducted a historical matched cohort study based on a nationwide population of nulliparous women born in 1947 to 2000 and living in Denmark during 1977 to 2018 (N=549,197). The data were obtained from the Danish Civil Registration System, the Danish National Patient Registry, the Fertility Register, and Statistics Denmark. Women who had a hysterectomy performed in 1977 to 2018 were included in the study (n=9535). For each of these women we randomly retrieved five nonhysterectomized women matched on age and calendar year to constitute the reference group (n=47,370). Cox proportional hazard regression analyses were performed to compare the risk of pelvic organ prolapse surgery in the 2 groups of women. Results: The study included 56,905 women whom we observed for up to 42 years, entailing 809,435 person-years in risk. Overall, 9535 women who underwent a hysterectomy were matched individually with 47,370 reference women. Subsequently, a total of 29 women (30.4%) who underwent a hysterectomy and 85 reference women (17.9%) had a pelvic organ prolapse surgery performed, corresponding to incidence rates of 20.5 and 12.7 per 100,000 risk years, respectively. In addition, the risk of pelvic organ prolapse surgery increased by 60% in women who underwent a hysterectomy compared with women in the reference group (crude hazard ratio, 1.6; 95% confidence interval, 1.0–2.5; P=.04; adjusted hazard ratio, 1.6; 95% confidence interval, 1.0–2.5; P=.04). After the exclusion of women who underwent vaginal hysterectomy and their matches, the results were significantly the same (crude hazard ratio, 1.5; 95% confidence interval, 1.0–2.4; P=.05). Furthermore, we found higher rates of pelvic organ prolapse surgery in women who had a subtotal hysterectomy, total hysterectomy, or vaginal and laparoscopic-assisted vaginal hysterectomies than in women in the reference group. Conclusion: Hysterectomy increased the risk of pelvic organ prolapse surgery for nulliparous women by 60%. Previous studies of multiparous women have similarly shown an increased risk of prolapse after hysterectomy. As the most common risk factor for pelvic organ prolapse—vaginal birth—was not included and women were >72 years of age in this study, the numbers of pelvic organ prolapse surgeries were low. Despite the low absolute risk of pelvic organ prolapse surgery in nulliparous women, they were important in investigating the association between hysterectomy and pelvic organ prolapse, excluding vaginal birth, which is the most common risk factor for pelvic organ prolapse. As this cohort study of nulliparous women found an increased risk of pelvic organ prolapse surgery after hysterectomy, it is implied that the uterus per se protects against pelvic organ prolapse. As such, gynecologists should be aware of the risks associated with hysterectomy, and alternative uterus-sparing treatments should be considered when possible. Furthermore, women should be informed about the risks before being offered a hysterectomy.