<b><i>Objective:</i></b> To estimate the procedure-related risk of miscarriage in pregnancies undergoing amniocentesis (AC) following inconclusive results for a chorionic villus sampling (CVS). <b><i>Methods:</i></b> This was a multicentric retrospective cohort study of patients in which both CVS at 11–13 weeks’ gestation and AC at 16–22 weeks were performed between January 1st, 2008, and July 31st, 2017. The primary outcome measure was pregnancy loss prior to 24 weeks gestation; the secondary one was intrauterine demise after 24 weeks. <b><i>Results:</i></b> A total of 287 patients underwent transabdominal CVS and AC. Nine patients were lost at follow-up; therefore, the analysis was conducted on a population of 278 patients (275 singletons and 3 dichorionic twin pregnancies). AC was performed because of placental mosaicism (93.6%), failure of direct/semidirect preparation of trophoblastic cells (3.2%), or targeted genetic testing after the diagnosis of an anomaly in the second trimester (3.2%). In continuing pregnancies, there were no fetal losses prior to 24 weeks’ gestation. Two intrauterine demises (including 1 fetus with multiple anomalies and growth restriction) in the third trimester were recorded. <b><i>Conclusion:</i></b> Patients undergoing midtrimester AC because of an inconclusive result of CVS can be reasonably reassured that in general the risk of miscarriage and fetal loss following the procedure is very small.