Primary mediastinal large B cell lymphoma (PMBCL) is an uncommon aggressive type of non-Hodgkin lymphoma. Rituximab-containing chemoimmunotherapy ± radiation therapy (RT) is standard first-line treatment. Relapsed or refractory (R/R) disease has long been treated with salvage chemotherapy followed by high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) in appropriate patients. We retrospectively analyzed all patients with R/R PMBCL treated with HDC/ASCT at our center between January 2000 and August 2022. Sixty patients received rituximab-BEAM (N=37) or rituximab-gemcitabine/busulfan/melphalan (R-GemBuMel) ± vorinostat (N=23), with ASCT. Forty-six patients received mediastinal RT, either as prior consolidation of frontline therapy or following ASCT. At median follow-up of 6 years (range, 0.3-21), the 5-year progression-free survival (PFS) and overall survival (OS) rates of the whole group are 58% and 77%, respectively, 51% and 65%, respectively, for R-BEAM patients, and 69% and 82%, respectively, for R-vorinostat/GemBuMel patients. Multivariable analyses showed that negative PET at ASCT [hazard ratio (HR), 0.28)] and involvement of only 1 organ (HR, 0.33) were independently associated with improved PFS. In addition, receiving R-vorinostat/GemBuMel (HR, 0.23) was an independent favorable predictor of OS. In conclusion, HDC/ASCT is effective in R/R PMBCL, with improved outcomes in patients receiving R-vorinostat/GemBuMel.