Aggressive non-Hodgkin's lymphoma (NHL), such as diffuse large B-cell lymphoma, can be cured in approximately 50% of cases, but those cases that recur and are not amenable to high-dose chemotherapy rely on palliative chemotherapy to improve symptoms and prolong life. Anthracyclines are associated with a high response rate in aggressive NHL but extended treatment results in cardiotoxicity. Liposomal encapsulated doxorubicin has been shown in other tumor types to allow for extended treatment with doxorubicin, but is associated with a low cardiac risk. The present study aimed to assess the response rate, survival and cardiac risk of patients with relapsed aggressive NHL treated with liposomal encapsulated doxorubicin. Eighteen patients with relapsed aggressive NHL were treated with liposomal encapsulated doxorubicin (40 - 50 mg/m2) for a planned six cycles. Some 83% of patients had diffuse large B-cell or mantle cell NHL. Four patients had a partial response (23%), whereas five patients had stable disease. None had a complete response. Eight patients progressed when receiving the liposomal encapsulated doxorubicin therapy. The median survival time was 34 weeks, and the median progression-free survival was 15.7 weeks. Overall survival was 50% at 6 months and 39% at 12 months. Progression-free survival was 33% at 6 months and was 28% at 12 months. The mean ejection fraction pre- and post-liposomal encapsulated doxorubicin treatment remained the same. Only one patient had a drop in ejection fraction to <50%. Liposomal encapsulated doxorubicin offers another choice to patients seeking palliation from their lymphoma recurrence with a response rate of 23% that was well tolerated and had a minimal cardiotoxic risk.