Intra-amniotic injection of digoxin is a well-known method for feticide before inducing a termination of pregnancy (TOP) at 17-24weeks of gestation. Information on its effectiveness when administered after 24weeks of gestation is limited. This study evaluated the efficacy of intra-amniotic digoxin injection for inducing fetal demise within 18-24hours, at 21-30weeks of gestation, and its safety. Prospective cohort study. Tertiary university medical centre. Women at 21-30weeks of gestation with a singleton pregnancy, admitted for TOP. Intra-amniotic injection of 2mg of digoxin was performed 1day before medical TOP. Fetal heart activity was evaluated by ultrasound for 18-24hours after the injection. Serum digoxin level and maternal electrocardiogram (ECG) were evaluated 6, 10, and 20hours after injection. Frequency of successful fetal demise. Fifty-nine women participated in the study. The mean gestational age was 24+2 weeks (range 21+0 -30+0 ), with 29 (49.2%) beyond 24+0 weeks of gestation. Fetal cardiac activity arrest was achieved in 55/59 cases (93.2%). Normal maternal ECG recordings were noted in all cases. Mean serum digoxin levels 6 and 10hours after injection were in the therapeutic range (1.3±0.7ng/l and 1.24±0.49ng/l, respectively) and below the toxic level (2ng/l). Extramural delivery following digoxin did not occur. There were no cases of chorioamnionitis. Intra-amniotic digoxin for feticide at 21-30weeks of gestation in a singleton pregnancy appears effective and safe before TOP at advanced gestational ages. This study shows that feticide by intra-amniotic digoxin injection at 21-30weeks of gestation appears effective and safe.