The clinical impact of MLL partial tandem duplication (MLL-PTD) was evaluated in 238 adults aged 18 to 59 years with cytogenetically normal (CN) de novo acute myeloid leukemia (AML) who were treated intensively on similar Cancer and Leukemia Group B protocols 9621 and 19808. Twenty-four (10.1%) patients harbored an MLL-PTD. Of those, 92% achieved complete remission (CR) compared with 83% of patients without MLL-PTD (P=.39). Neither overall survival nor disease-free survival significantly differed between the 2 groups (P=.67 and P=.55, respectively). Thirteen MLL-PTD(+) patients relapsed within 1.4 years of achieving CR. MLL-PTD(+) patients who relapsed more often had other adverse CN-AML-associated molecular markers. In contrast with previously reported studies, 9 (41%) MLL-PTD(+) patients continue in long-term first remission (CR1; range, 2.5-7.7 years). Intensive consolidation therapy that included autologous peripheral stem-cell transplantation during CR1 may have contributed to the better outcome of this historically poor-prognosis group of CN-AML patients with MLL-PTD.