To evaluate the efficacy of surgical management combined with chemotherapy in the treatment of drug-resistant gestational trophoblastic neoplasm (GTN) patients, and investigate factors influencing the outcome of the surgery combined with chemotherapy.Medical records of 42 patents with drug-resistant GTN who were treated by chemotherapy combined with surgical management at Peking Union Medical College Hospital from Jan 1996 to Jan 2006 were reviewed.Among 42 patients, 32 achieved serologically complete remission (SCR) with an SCR rate of 76%, and 10 patients had a treatment failure. Treatment failure was more frequently seen in patients who also had metastasis of other sites except for lungs and vagina and patients with antecedent non-molar pregnancy (P = 0.023 and 0.017, respectively). Preoperative human chorionic gonadotropin-beta subunit (beta-hCG) titer > 10 U/L (P = 0.020), failure to reach normal serum titers of beta-hCG during treatment (P = 0.003), age > or = 35 years (OR: 12.6, 95% CI: 2.4 - 66.0, P = 0.002) and preoperative chemotherapy regimens > or = 4 (OR: 4.5, 95% CI: 1.0 - 20.1, P = 0.059) were also correlated with treatment failure. All the 10 patients with treatment failure had at least 3 of 6 above mentioned predictors of treatment failure.Surgical management combined with chemotherapy is effective in the treatment of drug-resistant GTN. Age > or = 35 years, antecedent non-molar pregnancy, metastasis of other sites except for lungs and vagina, preoperative beta-hCG titer > 10 U/L, failure to reach normal serum titers of beta-hCG during treatment, and preoperative chemotherapy regimens > or = 4 are significant predictors of treatment failure. Patients with 3 or more predictors of treatment failure usually have poor prognosis. Therefore, surgical management should not be performed for these patients.