Objective To report our recent experience managing ultra-high-risk gestational trophoblastic neoplasia (GTN) patients with liver and brain metastases. Design A retrospective review of data from a national gestational trophoblastic disease centre. Setting The Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China. Sample Total of 298 GTN patients recruited from January 2014 to December 2017. Main outcome measures The CR rate and drug-resistance rate after initial treatment of ultra-high-risk GTN patients with liver or brain metastases. Methods The clinical characteristics and treatment and prognosis outcomes in 11 ultra-high-risk GTN patients with liver or brain metastases were performed by descriptive analyses. The prognostic factors for death in all GTN patients were identified by Cox proportional hazards regression. Survival analysis were used to analyze survival time between GTN patients stratified according to liver or brain metastases. Results. The CR rate and drug-resistance rate after initial treatment of ultra-high-risk GTN patients with liver or brain metastases was 0% and 90.9% respectively, but the 5-year OS rate was 81.8% (n=11). Liver metastases (hazard ratio [HR]: 34.05; 95% confidence interval [CI]: 1.65–703.7; P=0.02) and brain metastases (HR: 49.19; 95% CI: 5.6–432.1; P<0.01) were independently significant risk factors for death in all GTN patients. Conclusions. Liver and brain metastases were found to be independently significant risk factors for death in all GTN patients. The drug-resistance rate with initial treatment was 90.9% in ultra-high-risk GTN patients with liver or brain metastases.