Objectives: To evaluate the safety and relative effectiveness of two common techniques to achieve fetal asystole prior to second trimester surgical termination of pregnancy. Methods: We recruited 268 women age 18-42 years who desired surgical pregnancy termination between 20 and 24 weeks gestation at a single Planned Parenthood in Los Angeles. Participants were randomly assigned to receive intrafetal (n=135) or intra-amniotic (n=131) digoxin 1mg on the day of laminaria placement. Presence or absence of fetal cardiac activity was documented on the morning of dilation and evacuation. The primary outcome was rate of fetal asystole. Secondary outcomes included adverse events, side effects and procedure differences. Results: Participants were young (mean 24.9 years, SD 5.9), Hispanic (53%) and parous (median parity 1, range 0-7 births), with a mean gestational age of 21+4 weeks. The rate of fetal asystole was higher in the intra-fetal group (95%) than the intra-amniotic group (82%; RR of asystole 3.97, 95% CI 1.6 – 9.6). Overall there were fewer adverse events in the intrafetal (3%) group than in the intra-amniotic (9%) group (RR of complication .33, 95% CI .10 – 1.06), including a lower risk of extramural delivery (RR .47, 95% CI .08 – 2.6). There were no differences in neurological, cardiac, or gastrointestinal side effects. There were no differences in injection duration, operative time or blood loss. Conclusion: Intrafetal injection of digoxin had a higher rate of fetal asystole than intra-amniotic injection, with fewer adverse events and no differences in side effects or procedure time.