With increasing therapeutic alternatives available, there is growing interest in tools that accurately identify patients most suitable for intensive acute myeloid leukemia (AML) chemotherapy. Nowadays, conceptual criteria proposed by an Italian panel of experts are widely used for this purpose. How accurately these Ferrara criteria predict fitness for intensive chemotherapy is unknown.We assessed the fitness of adults undergoing intensive AML therapy based on Ferrara criteria and determined the accuracy of this assessment for early mortality and survival prediction.Among 655 adults who received curative-intent induction or reinduction chemotherapy with 7 days of standard-dose cytarabine and 3 days of an anthracycline ("7+3") CLAG-M (cladribine, high-dose cytarabine, granulocyte colony-stimulating factor, and mitoxantrone), or reduced-dose CLAG-M, 197 (30%) met at least one of the criteria defining unfitness for intensive chemotherapy (F-unfit). Compared with F-fit patients, the overall survival of F-unfit patients was significantly shorter (median, 4.8 months; 95% CI, 3.6 to 6.5 months v 36.8 months; 95% CI, 27.4 to 73.0 months; P < .001). When used alone, the Ferrara unfitness assessment was more accurate in predicting day 28 and day 100 mortality than the treatment-related mortality score we developed previously (used binary, ≤ 13.1 v > 13.1), as indicated by area under the receiver operating characteristic curve (AUC) values of 0.76 and 0.79 versus 0.66 and 0.62. The predictive accuracy of the Ferrara unfitness assessment could be significantly improved by including additional covariates such as performance status and albumin, yielding AUCs as high as 0.84-0.85 for the prediction of day 28 or day 100 mortality. Prediction of overall survival was less accurate, yielding a c-statistic value as high as 0.75 in multivariable models.Ferrara unfitness criteria provide a good prediction tool for shorter-term mortality after intensive AML chemotherapy. Our data may serve as a benchmark for expected outcomes with intensive chemotherapy in F-fit and F-unfit patients.