The open-label, prospective study aimed to evaluate the efficacy and safety for standard intensive chemotherapy compared with attenuated therapy in elderly patients with acute myeloid leukemia (AML). A total of 297 patients between 65 and 82 years were enrolled in the study. The 141 patients received standard-dose therapy (daunorubicin 45 mg/m(2) × 3 days with cytarabine 100 mg/m(2) × 7 days for induction therapy, while post-induction therapy consisted of high-dose cytarabine 1.5 g/m(2) × 4 days), and the attenuated treatment (daunorubicin 30 mg/m(2) × 3 days with cytarabine 75 mg/m(2) × 7 days for induction therapy, while post-induction therapy consisted of attenuated high-dose Ara-C 1.0 g/m(2) × 3 days) was administered to the remaining 156 patients, based on a random number assigned. Total 168 patients (56.6%) achieved complete remission with an incomplete blood recovery (CR)/CRi. No significant differences were observed between the two treatments (P = 0.60). Attenuated chemotherapy improved overall survival (OS) and progression-free survival (PFS) compared to standard-dose therapy; 5-year OS values for these two groups were 39 and 24 months, respectively (P < 0.001), and the PFS values for these two groups were 35 versus 23 months (P < 0.001). In addition, the attenuated treatment with a poor risk profile overcame the negative impact and yielded OS and PFS values similar to those of the standard-dose chemotherapy with a better-to-intermediate risk profile. Five-year OS values for these two groups were 28 versus 28 months (P = 0.89), and the 5-year PFS values were 27 and 28 months, respectively (P = 0.89). The most common adverse drug effect for chemotherapy was agranulocytosis (98.3%). There was a significant difference in early mortality between the attenuated and standard-dose treatment groups (0.64% vs. 7.1%, respectively, P < 0.01). Standard intensive chemotherapy is less effective and far more toxic than attenuated induction and post-induction regimen in elderly patients with AML.