We investigated whether etoposide might be a suitable alternative to anthracyclins for the treatment of elderly patients with acute myeloid leukemia (AML) in whom anthracyclins are contraindicated. In total, 88 patients over 60 years old were treated in our department between 1988 and 2000 for de novo or secondary AML. Of these 88 patients, 21 had severe cardiac disease and received a combination of etoposide and cytosine arabinoside (group A). They were compared with 23 patients who received daunorubicin plus cytosine arabinoside (group B) and 44 patients who received mitoxantrone, cytosine arabinoside and etoposide (group C). In group A, the complete remission (CR) rate was 33% (7/21), median disease-free survival (DFS) was 365 days and median overall survival (OS) was 214 days. These results were not statistically different from those for the anthracyclin-based regimens (CR 43%, DFS 210 days, OS 150 days for group B and CR 47%, DFS 216, OS 295 days for group C). Moreover, there was no significant difference in the number of treatment-related toxic events and deaths in the 3 treatment groups. Etoposide combined with a standard dose of cytosine arabinoside is relatively safe and effective in elderly patients with AML and offers an alternative approach to patients with cardiac contraindications to anthracyclin treatment.