Termination of pregnancy in the second trimester for an intrauterine death of a fetus with anencephaly in a woman with previous three cesarean sections is a difficult clinical dilemma. A 34-year-old, gravida 4, para 3 woman was admitted at 20 weeks gestation for termination of pregnancy due to intrauterine death of a fetus with anencephaly. She had had three previous cesarean sections. She received two doses of 200 mcg misoprostol tablets vaginally 12 hours apart. Then two doses of 400 mcg misoprostol tablets were given vaginally 12 hours apart. There were no uterine contractions or cervical changes. Finally, she received five doses of 400 mcg misoprostol tablets vaginally every eight hours. The patient responded after the last dose and the fetus with the placenta aborted completely without complications. The estimated blood loss was 200 ml. Conclusion: Misoprostol can avoid hysterotomy for termination of pregnancy in the second trimester with history of previous three cesarean sections and an intrauterine death of a fetus with anencephaly.