The prognosis of acute myeloid leukemia (AML) in older adults is generally poor. Standard cytotoxic chemotherapy is usually poorly tolerated and provides dismal results in this patient population. Gemtuzumab ozogamicin (GO) is an immunoconjugate that has activity in the relapsed and refractory setting. We hypothesized that administering this agent, as an initial treatment in AML patients over the age of 65 would have, at least, similar efficacy to standard therapy, but at much less toxicity. We report on the first 12 patients that were treated solely with GO as induction, consolidation, and maintenance therapy as part of a single institution clinical trial. The treatment was well tolerated, with a response rate of 27%. Toxicities were acceptable, although five patients (41%) developed cardiac toxicity three of which had grade 3 and/or 4. Responses were present regardless of the karyotype, and lasted for a median of 7.6 months. These early results suggest that the option of single agent monoclonal antibody therapy is viable in this patient population and that additional studies are warranted with this agent either alone or in combination as initial therapy.