Open AccessBackground: Older patients with cardiac problems and diagnosis of diffuse large B-cell lymphoma generally are treated with reduced-dose chemotherapy and anthracyclines, the best drug in this malignancy, generally is omitted. Thus, survival is very poor in this setting of patients (< 20% at 3 years). Pegylated liposomal doxorubicin (PLD) has been showed clinical activity in younger patients and without excessive cardiac toxicity. Methods: Thus, we began an open label in 69 frail patients (age > 65 years, and with diagnosis of cardiac abnormalities), employed a CHOP-like-regimen, with PLD, 30 mg/m2, instead of doxorubicin. Sixty-nine patients were enrolled, in intent to treat analysis all were available for efficacy and toxicity. Results: Complete response was achieved in 52 cases (72%). Three patients were excluded for non-hematological toxicity, and 9 patients relapsed, thus with a median follow-up of 73 months (range 64 to 110 months), actuarial curves at 5-years showed that relapse free survival was 78% (95% confidence interval (CI): 69% to 85%) and overall survival was 79% (95% CI: 71% to 85%). Although severe granulocytopenia was observed in 5.6% of cycles, no death was observed. Two patients die secondary to myocardial ischemia and 10 patients worsened the left ejection ventricular function, but only 3 developed clinical dates of congestive heart failure. Conclusions: We considered that the use of PLD is an effective and safe drug in the treatment of these special setting of patients with the end-point of treatment is cure.