Objective To assess the efficacy and safety of in-utero aspiration (IUA) of anechoic fetal ovarian cysts. Methods This multicenter, prospective, randomized open trial in two parallel groups included women from nine outpatient fetal medicine departmentswith singleton pregnancy >= 28 weeks of gestation and a female fetus with an ultrasound-diagnosed simple ovarian cyst, defined as a single fully anechoic cystic structure measuring >= 30 mm. They were allocated randomly to IUA under ultrasound guidance or expectant management. All procedures were performed by trained senior obstetricians. Primary outcome was need for neonatal intervention, by laparoscopy, laparotomy or transabdominal aspiration. Secondary outcomes were in-utero involution of the cyst and oophorectomy at birth. Analyses were conducted according to the intention-to-treat principle. Results Of 61 participants, 34 were allocated to IUA and 27 to expectant management. Three IUA procedures (9%) could not be performed (one due to fetal position and two due to aspirations being dry). The remaining 31 IUA procedures were uneventful. The incidence of neonatal intervention did not differ significantly between the IUA and the expectant management groups (20.6% vs 37.0%; relative risk (RR), 0.55; 95% CI, 0.24-1.27). Nonetheless, IUA was associated with increased incidence of in-utero involution of the cyst (47.1% vs 18.5%; RR, 2.54; 95% CI, 1.07-6.05) and reduced rate of oophorectomy (3.0% vs 22.0%; RR, 0.13; 95% CI, 0.02-1.03) compared with expectant management. Conclusion IUA of anechoic fetal ovarian cysts, compared with expectant management, was not associated with a reduction in overall neonatal interventions but was associated with a reduced oophorectomy rate.