OBJECTIVE: To observe the efficacy and safety of methotrexate in the interventional treatment of cesarean scar pregnancy (CSP). METHODS: 40 CSP women were randomly divided into control group (20 cases) and observation group (20 cases). Control group pregnant women received methotrexate 1 mg/kg, intramuscular injection, once a day; mifepristone 25 mg, orally, twice a day, for 5 d. Observation group pregnant women received methotrexate 50 mg, gelatin sponge embolization was conducted after uterine artery injection. Human chorionic gonadotropin (β-HCG) value was detected after administration, then curettage was conducted until β-HCG value decreased to less than or equal to 2 000 U/L; pregnant women still received mifepristone 25 mg if β-HCG value was higher than 2 000 U/L, then curettage was conducted until β-HCG value decreased to less than or equal to 2 000 U/L. The amount of bleeding, time distance to curettage, the time of β-HCG value to normal in 2 groups were observed, and the incidence of adverse reactions was recorded. RESULTS: The amount of bleeding in observation group was significantly lower than control group, time distance to curettage and the time of β-HCG value to normal were significantly shorter than control group, with statistical significances(P<0.05). And there were no obvious adverse reactions in 2 groups. CONCLUSIONS: Methotrexate can effectively reduce the bleeding in the interventional treatment of CSP, shorten the time distance of diagnosed to curettage and the time of β-HCG value to normal, with good safety.