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