> Objective: To evaluate the efficacy and safety of two different methods, intravenous prostaglandin E2 and extraamniotic prostaglandin F2alpha instillation, in second-trimester pregnancy termination. Methods: We designed a prospective randomized longitudinal study. 130 consecutive patients with various indications for second-trimester pregnancy termination were recruited. Patients were managed randomly with either intravenous continuous prostaglandin E2 infusion or extraamniotic prostaglandin F2alpha instillation. Laminaria were inserted in patients with unfavorable cervixes. The instillation-abortion time, success rate within 24 hours, dosage of both medications, and side effects were recorded and analyzed. Results: There was a significantly shorter instillation-abortion time (11.85 +/- 9.65 versus 22.18 +/- 16.83 hours, P < 0.001), higher complete abortion rate (71.91% versus 41.5%, P = 0.013), and a higher rate of successful abortion within 24 hours (87.6% versus 56.1%, P < 0.001) in patients treated with intravenous prostaglandin E2 than in those with extraamniotic prostaglandin F2alpha. Conclusions: Prostaglandin E2 had a higher rate of successful abortion and fewer side effects than prostaglandin F2alpha. This implies that intravenous prostaglandin E2 might be a better choice for second-trimester pregnancy termination compared with extraamniotic prostaglandin F2alpha.