Addition of gemtuzumab ozogamicin (GO) to induction chemotherapy improves outcomes in older patients with acute myeloid leukemia (AML) but it is uncertain whether a fractionated schedule provides additional benefit to a single dose. We randomised 852 older adults (median age 68yrs) with AML/high risk myelodysplasia to GO on day 1 (GO1), or on days 1 and 4 (GO2) of course-1 induction. Median follow-up was 50.2 months. While complete remission rates post course 1 did not significantly differ between arms (GO2 63%, GO1 57%, OR 0.78 (0.59-1.03), P=0.08), there were significantly more patients who achieved CR with MRD <0.1% (50% vs 41% OR 0.72 (0.54-0.96) P=0.027). This differential MRD reduction with GO2 varied across molecular subtypes being greatest for IDH mutations. 5yr overall survival (OS) was 29% for GO2 and 24% for GO1 patients (HR 0.89, P=0.14). In a sensitivity analysis excluding patients found to have adverse cytogenetics /TP53 mutations, 5yr OS was 33% for GO2 and 26% for GO1 (HR 0.83, P=0.045). 228 (27%) patients received an allo-transplant in first remission. OS was superior for transplanted patients on the GO2 arm (HR 0.67, 95%CI 0.47-0.97, P=0.033) however this benefit was lost when patients were censored at transplant. In conclusion, GO2 was associated with greater reduction in MRD and improved survival in older adults with non-adverse risk genetics. This benefit from GO2 was dependent on allo-transplant to translate the better leukemia clearance into improved survival. CT# ISRCTN 31682779.