Non-pegylated liposomal doxorubicin (NPLD) has demonstrated antitumour activity equivalent to conventional doxorubicin and a significantly lower risk of cardiotoxicity. This phase II trial was performed to evaluate the activity and the safety of NPLD and ifosfamide combination in patients with metastatic soft tissue sarcoma. Thirty-four patients received NPLD 40 mg/m(2) (d1) and ifosfamide 3 g/m(2)/day (d1-3) every three weeks as first-line therapy of metastatic soft tissue sarcoma. The treatment was planned for a maximum of six cycles. The objective response (OR) rate among response-assessable patients was 55.9%. The median progression-free survival (PFS) was 4.2 months and the median overall survival (OS) was 11.2 months. Symptomatic grade 3 cardiotoxicity occurred in one patient (3%). The combination of NPLD and ifosfamide reported in a population of metastatic soft tissue sarcoma patients at risk for developing heart failure encourage antitumour activity, similar to that of classical doxorubicin.