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In the present exploratory, observational study, we compared the effect of intensive versus nonintensive treatment on quality of life for patients aged ≥ 60 years diagnosed with acute myeloid leukemia or high-risk myelodysplastic syndrome at 1 month after treatment.A total of 73 patients with acute myeloid leukemia or high-risk myelodysplastic syndrome who had been treated at the inpatient and outpatient malignant hematology at Moffitt Cancer Center, a National Cancer Institute-designated comprehensive cancer center, were included. Two paired measurements of self-reported quality of life were used, 1 before treatment and 1 at 1 month after treatment to compare intensive versus nonintensive treatment. Patients completed the Functional Assessment of Cancer Therapy–Leukemia version for the quality-of-life measurement. Repeated measures analysis of variance was used to compare the effect of treatment and time and the interaction of treatment and time. The main research variables were intensive versus nonintensive treatment as the independent variable and quality of life measured using the Functional Assessment of Cancer Therapy–Leukemia version as the dependent variable.Physical function and leukemia symptoms improved for patients treated with intensive chemotherapy. A trend was found for improved quality of life for the intensive treatment compared with nonintensive treatment, for which the quality of life was stable at 1 month.The study participants treated with inpatient, induction chemotherapy experienced statistically significant improvement in their quality of life at 1 month. The outpatient, nonintensive study participants had stable quality of life at 1 month.The results of the present pilot study can be used to counsel older patients with acute myeloid leukemia and high-risk myelodysplastic syndrome regarding treatment choices that will align with their goals for their quality of life. Future studies are needed with a larger and more diverse patient sample to address whether the more intensive treatment approach improves patients’ quality of life.