Autologous stem cell transplant (ASCT) is the standard of care for patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adding rituximab (R) to the initial therapy has improved outcomes; however, the benefit of ASCT for chemosensitive patients who fail R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, prednisone) is unclear. Patients who underwent ASCT between 1997 and 2006 for DLBCL at two partner institutions were identified. Characteristics and outcomes were compared between patients who received R-CHOP as initial chemotherapy and those who received CHOP. Of the 185 patients evaluated, 137 were initially treated with CHOP and 48 received R-CHOP. Patients who received R-CHOP were older, had shorter remissions, and initially had more advanced stage. With univariate analysis, PFS and OS did not differ; however, multivariable Cox regression analysis suggested a poorer prognosis for patients who underwent ASCT after failing R-CHOP. In conclusion, patients who fail R-CHOP appear to benefit from ASCT, but they may have a worse prognosis compared to patients who fail CHOP alone.