Patients diagnosed with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL) may achieve prolonged survival following receipt of high-dose chemotherapy/autologous stem cell transplantation (HDC/ASCT) or CD19-directed chimeric antigen receptor modified T cell therapy (CART19). Although early results from randomized clinical trials suggest that assignment to CART19 versus salvage immunochemotherapy as second-line therapy results in improved survival, analysis of a large series of patients who actually received HDC/ASCT or CART19 has yet to be performed. Such an analysis may inform future research efforts to optimize the risk stratification of R/R DLBCL/HGBL patients who are candidates for either therapy. The aim of this study was to evaluate clinicopathologic factors predictive of freedom from treatment failure (FFTF) for R/R DLBCL/HGBL patients following receipt of HDC/ASCT or CART19, and to compare patterns of treatment failure (TF) in R/R DLBCL/HGBL patients receiving HDC/ASCT and those receiving CART19. THE STUDY GROUP COMPRISED: patients age ≤75 years with R/R DLBCL/HGBL who received HDC/ASCT demonstrating partial or complete metabolic response to salvage immunochemotherapy and/or CART19 in the standard of care setting at the University of Pennsylvania between 2013 and 2021. Survival analyses were performed from the time of infusion of either HDC/ASCT or CART19, as well as at landmark time points postinfusion for patients who achieved FFTF. For 100 HDC/ASCT patients with a median follow-up of 62.7 months, the estimated 36-month FFTF and overall survival (OS) rates were 59% and 81%, respectively. For 109 CART19 patients with a median follow-up of 37.6 months, the estimated 36-month FFTF and OS rates were 24% and 48%, respectively. HDC/ASCT patients had significantly higher rates of estimated 36-month FFTF when they achieved actual FFTF at 3, 6, 12 and 24 months. Additionally, the rates of baseline characteristics predictive of TF at 36 months for either HDC/ASCT or CART19 patients were either similar to or significantly lower for CART19 patients compared to HDC/ASCT patients who achieved actual FFTF at 3, 6, 12, and 24 months. Patients with R/R DLBCL/HGBL achieving response to salvage immunochemotherapy who received HDC/ASCT had a high rate of estimated FFTF regardless of whether they harbored features predictive of resistance to salvage immunochemotherapy, which may be more durable than that of R/R DLBCL/HGBL patients receiving CART19. These findings support further investigation of disease characteristics, such as molecular features, that may predict response to salvage immunochemotherapy in patients fit for HDC/ASCT.