BACKGROUND: Survival after high-dose chemotherapy (HDCT) as second-salvage treatment (SST) in multiple relapsed germ-cell tumors (GCTs). PATIENTS AND METHODS: Existing databases in Berlin and Marburg of HDCT trials from 1989 to 2008 were retrospectively screened. Among 534 patients, 71 of 534 (13%) patients were scheduled for HDCT having failed previous conventional-dose first-line and first-salvage chemotherapy regimens; those 49 patients who had received at least cisplatin plus etoposide first-line as well as conventional-dose cisplatin-based first-salvage regimens and were diagnosed after 1 January 1990 were further analyzed. RESULTS: Median age at SST was 32 years (range 19-52 years). Median follow-up for surviving patients was 4 years (range 1.7-8.5 years). Three of 49 (6%) patients either progressed or died before scheduled HDCT; the remaining 46 of 49 (94%) received either single or sequential HDCT. The rate of favorable responses to HDCT was 27 of 49 (55%). Nine patients remain alive and free of progression. One additional patient was lost to follow without progression at 4 years. The projected overall survival rate at 5 years was 17% (95% confidence intervals 7% to 30%). CONCLUSION: HDCT can induce remissions in patients with multiple relapsed GCTs with a long-term survival rate of approximately 17%.