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Objective: To compare the efficacy and safety of medical abortion of different regimens for termination of pregnancy at 8-16 weeks of gestation. Methods: Healthy pregnant women requesting medical abortion at 8-16 weeks' gestation within 12 hospitals in Shanghai were randomly allocated to four treatment groups. Three intervention groups were given mifepristone 200 mg as a single dose then 24 h later misoprostol 600 μg at 3 h intervals vaginally, orally or vaginally followed by orally, respectively. Control group was given mifepristone 100 mg for 2 d, followed at 48 h by initiation of misoprostol 600 μg vaginally every 12 h. The primary outcome measures were the successful abortion rate, the induction-to-abortion interval, vaginal bleeding and side effects. Results: Efficacy outcomes were analyzed for 1 112 women (92.67%), excluding 88 protocol violations. Termination successful rates were similar among the four groups from 97.1% to 97.8%. The average dose of misoprostol and the incidence of side effects in control group were lower than those in three intervention groups. Stratified analysis showed that the interval of induction-to-abortion at gestation of 11-16 weeks was decreased in control group. Conclusion: The four regimens have the similar termination successful rates in spite of different administration intervals or routes. Control group was recommended for the advantages of reduced dose of misoprostol and fewer side effects. © 2013 The Editorial Board of Journal of Reproduction and Contraception., SCOPUS: ar.j, info:eu-repo/semantics/published