DHAP (dexamethasone, cytosine arabinoside and cis-platinum) is a commonly used regimen for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The optimal treatment for patients who do not respond to DHAP, but are still potential candidates for autologous stem cell transplantation, is unclear. One option is to proceed with an alternative chemotherapy regimen such as ifosfamide, carboplatin, and etoposide (ICE). The overall response rate (ORR) and overall survival (OS) associated with this chemotherapy sequence is unknown. Patients with DLBCL receiving DHAP as the first salvage therapy without response followed by ICE as second salvage were studied to learn the ORR to ICE and OS. The ORR to ICE in these DHAP-failures was 52% (11/21) with 14% (3/21) complete responses and 38% (8/21) partial responses. Nine patients (43%) were able to proceed to transplant and 29% (6/21) are long-term survivors. In patients with stable disease after DHAP the ORR was 67% (8/12) with 42% (5/12) becoming long-term survivors. In contrast, only 33% (3/9) of patients who had progressive disease on DHAP responded to ICE with only one patient achieving a durable response. Patients with stable disease after DHAP can be salvaged with ICE-based chemotherapy regimens whereas patients who progress on DHAP have a poor outcome. Patients with progressive disease on DHAP should be considered for alternative salvage regimens or experimental therapy.