The aim of this study was to evaluate the results with novel drug combination consisting of paclitaxel and carboplatin (PC) for salvage of refractory high-risk gestational trophoblastic neoplasia (GTN) previously treated with EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristine) and EMA-EP (etoposide, methotrexate, actinomycin, and cisplatin) regimens. This was a prospective study conducted at a regional cancer institute from 2008 to 2012. The study group received the combination of paclitaxel (175 mg/m) and carboplatin (area under the curve, 6) intravenously every 3 weeks. After undetectable β-subunit of human chorionic gonadotropin values are achieved, 2 courses of additional chemotherapy were administered to reduce the risk of relapse. They were followed up and assessed by clinical examination, monthly β-subunit of human chorionic gonadotropin for a minimum of 24 months. The event-free survival and overall survival were calculated for all patients using Kaplan-Meier curve (SPSS version 19; SPSS Inc). A total of 65 persistent GTN patients were treated during the study period. Eight (12.3%) of 65 patients having refractory GTN were treated with PC regimen. The initial International Federation of Gynecology and Obstetrics staging in the study group was stage I disease in 1 (12.5%), stage III in 4 (50%), and stage IV in 3 (37.5%) patients. According to the World Health Organization prognostic risk scores, 1 patient was in the low-risk group (12.5%), and 7 patients were in the high-risk group (87.5%). The study group received a total 35 courses of the combination PC. The median number of courses for each patient was 4.4. The complications include mucositis in 3 patients and thrombocytopenia, febrile neutropenia, and transient hepatic dysfunction in other patients. Six (75%) of 8 patients had good response, whereas 2 patients had progression. Five patients (62.5%) are in remission at median 30 months' follow-up, and 3 (37.5%) of 8 patients have died. The combination of paclitaxel and carboplatin (PC) regimen produces durable complete remission and manageable side effect profile in patients with refractory GTN previously treated extensively with frontline chemotherapies.