Objectives: To determine the temporal persistence of residual cell-free DNA (cfDNA) of deceased co-twin in maternal circulation after selective fetal reduction and evaluate its long-lasting effect on noninvasive prenatal testing (NIPT) results. Design: Prospective observational study Setting: The Third Affiliated Hospital of Guangzhou Medical University Population: Dichorionic diamniotic twins (n=5) underwent selective fetal reduction of a co-twin with trisomy. Methods: With consent, maternal blood was collected immediately before reduction and periodically after reduction until birth. CfDNA of each maternal blood sample was sequenced for NIPT and analyzed for fetal trisomies and fetal fractions. Main Outcome Measured: Detectable T-scores for trisomy identification and three types of fetal fractions including the total fetal fraction, the fetal fraction of the deceased co-twin, and the fetal fraction of the surviving co-twin.