A combination of 5-fluorouracil plus actinomycin D (5FU plus Act D) is the regimen that has been commonly administered to Chinese and Japanese gestational trophoblastic neoplasia patients as the first or second line of treatment with an excellent outcome. However, the efficacy of this regimen in a salvage setting was unclear. To evaluate the efficacy and safety of the 5 FU plus Act D regimen utilized in this condition, all GTN patients resistant to at least three previous chemotherapy regimens who received the 5 FU plus Act D regimen between August 2009 and January 2011 at Chiang Mai University Hospital were reviewed. There were five cases who met the criteria. Four of those patients were in FIGO stage III to IV with a WHO scoring of more than 12. The median number of cycles for each patient was two and only one case achieved remission while four of the cases were unresponsive. The toxicity was evaluated in 12 cycles. Common complications were uncomplicated myelosuppression and mucositis. In conclusion, this regimen revealed modest efficacy in a salvage setting with manageable toxicity.