To determine the efficacy of first-line sequential high-dose VIP chemotherapy (HD-VIP) in patients with primary mediastinal nonseminomatous germ cell tumours (GCT), 28 patients were enrolled on a German multicentre trial. High-Dose VIP chemotherapy consisted of 3-4 cycles of dose-intensive etoposide and ifosfamide plus cisplatin, q22days, each cycle followed by autologous peripheral blood stem cell transplantation plus granulocyte-colony stimulating factor (G-CSF) support. One cycle of standard-dose VIP was applied to harvest peripheral blood stem cells. Ten patients had mediastinal involvement as the only manifestation (36 %), 18 of 28 patients had additional metastatic sites, such as lung (n=17; 61%), liver (n=7; 25%), bone (n=5; 18%), lymph nodes (n=3; 11%) and CNS (n=3; 11%). Median follow-up was 43 months (range, 7-113) for all patients and 52 months (range, 22-113) for surviving patients. Nineteen of 28 patients obtained a disease-free status; 11 with HD-VIP alone and eight with adjunctive surgery. In addition, one of the four patients with marker negative partial remission after HD-VIP without resection of residual masses is currently alive. Two patients developed recurrence of GCT or teratoma. Two patients have died due to an associated haematologic disorder. The 2-year progression-free survival and overall survival rates are 64 and 68%, respectively. This report represents a subgroup analysis of 28 patients with mediastinal nonsemina within the German first-line study for 'poor prognosis' GCT. Compared to data of an international database analysis including 253 patients with mediastinal nonseminoma treated with conventional chemotherapy, the results may indicate that HD-VIP results in an approximately 15% survival improvement.