Objective To evaluate the efficacy and toxicity profile of floxuridine, dactinomycin, etoposide and vincristine (FAEV) regimen as primary treatment in stage IV gestational trophoblastic neoplasia (GTN). Methods From 2004 to 2014, FAEV was given to 30 stage IV GTNs as the primary treatment (at least two cycles) in Peking Union Medical College Hospital. Remission/resistance/recurrence rate, the cause of treatment failure, and the toxicity profile were analyzed. Results A total of 190 cycles of FAEV were administered to 30 patients; the median number of the cycles was 6 (range 3–11). The median follow up was 52.3 months (range 8–120). Of all the patients received FAEV primarily, 24 achieved complete remission after only received FAEV, with no recurrence; 6 patients later switched to EMA-CO treatment due to FAEV resistance. Among the 6 patients, 2 died of progressive disease after multiple lines of chemotherapy, the other 4 achieved complete remission after second–line or third-line chemotherapy and 1 of them relapsed 15 months later. FAEV was well tolerated. No one died from toxicity. Severe grade 4 neutropenia and thrombocytopenia were noted in 8 (26.7%) and 2 (6.7%) cases. No secondary malignancy was observed with follow-ups from 8 to120 months. Patients treated with FAEV showed good reproductive outcomes. Conclusions FAEV regimen might be considered as an alternative to other chemotherapy regimen in the primary treatment of stage IV GTN, where it had a high rate of remission and a tolerable toxicity.