The optimal post-remission therapy for patients in first complete remission (CR1) continues to be debated. Some centers choose to omit more intensive regimens, such as autologous or allogeneic transplantation, preferring to reserve these for treatment after relapse. Such strategies are mostly based on reports of treatment in second CR, but fail to account for the fact that most relapsed patients do not get into a second CR. The purpose of this retrospective study is to analyze the overall survival (OS) rate of AML patients from the date of first relapse. The data are based on the outcome of 2441 patients entered on 8 consecutive ECOG studies for newly diagnosed AML between 1983 and 1997. The studies included are E3483, PC486, E3993, E4995, E1490, E3997 and the two Intergroup studies E3489 and E2491 (INT0129). The data are arbitrarily divided among patients older or younger than 55 years, as this was the age used in most studies to distinguish between younger and older patients. Of 1699 patients ≤55 years, 1150 (68%) achieved CR1 and 402 (35%) relapsed. The median OS of these patients from first relapse was 6.4 months with a 5-year OS of 11%. If APL patients are excluded and the data are analyzed only by studies for young AML patients (less than age 55 or 60), the median OS from first relapse is 6.2 months with a 5-year OS of only 9%. In the US Intergroup Study (E3489) for patients ≤ 55 years, the median OS from first relapse after an allogeneic transplant, an autologous transplant or consolidation chemotherapy was 6.6, 5.2 and 8 months, respectively with a 5-year OS of 18%, 0% and 0%, respectively. The latter data, however, require cautious interpretation as the numbers in these subgroups are small. These data indicate that patients who relapse after standard initial AML therapy have a dismal OS from the time of relapse. Some die at relapse and only a minority achieve a second CR. Those refractory to reinduction therapy uniformly have a very poor prognosis. These data thus suggest that in planning post-remission therapies approaches most likely to lead to a prolonged leukemia-free survival should be offered rather than reserving such strategies following relapse. Survival from relapse.