Outcomes for diffuse large B-cell lymphoma (DLBCL) patients relapsing after autologous hematopoietic cell transplantation (auto-HCT) have been historically poor. We studied outcomes of such patients using data from 4 transplantation centers. Eligibility criteria included adult patients (age $18 years) with DLBCL experiencing disease relapse after auto- HCT performed during 2006 to 2015. The time period was stratified into 2 eras (era 1, 2006- 2010; era 2, 2011-2015). The primary end point was postrelapse overall survival (PR-OS). Secondary end points were factors prognostic of PR-OS. Of the 700 patients with DLBCL who underwent auto-HCT, 248 (35%) relapsed after auto-HCT. Median PR-OS of all relapsed DLBCL patients after auto-HCT (n 5 228) was 9.8 months (95% confidence interval [CI], 7-15). Median PR-OS was significantly better for patients in complete (17.8 months; 95% CI, 7.9- 41.6) vs partial remission at auto-HCT (7.1 months; 95% CI, 5.4-11; P 5 .01), those undergoing auto-HCT .1 year (12.8 months; 95% CI, 7.6-24.9) vs #1 year after DLBCL diagnosis (6.3 months; 95% CI, 4.5-9.2; P 5 .01), and those with late (56.4 months; 95% CI, 23.7-') vs early relapse (5.9 months; 95% CI, 4.5-8.8; P , .0001). On multivariate analysis, although late relapse (hazard ratio [HR], 0.21; 95% CI, 0.13-0.34; P , .0001) was associated with significantly lower mortality, the risk of mortality increased with age (HR, 1.25 per decade; 95% CI, 1.06-1.48; P 5 .009). This is the largest study to date to evaluate outcomes of DLBCL patients relapsing after auto-HCT. Our study provides benchmarking for future trials of chimeric antigen receptor T cells and other promising agents evaluating PR-OS after auto-HCT.