Background: The aim of this study was to evaluate the prognostic value of D-dimer in patients with newly diagnosed de novo non-M3 subtypes of acute myeloid leukemia (AML). Materials and Methods: We retrospectively analyzed the clinical data from 245 patients with newly diagnosed de novo non-M3 subtypes of AML at the Tongji Hospital from January 2010 to December 2014. Resuls: The comparison results indicated that the D-dimer values were higher in patients with AML with the following characteristics: WBC count >= 20 x 10(9)/L (2.20 versus 6.00, P = 0.001), percentage of bone marrow (BM) blasts >= 60% (2.06 versus 5.69, P = 0.003), and poor-risk stratification (P < 0.001). Cox univariate regression analysis showed that overall survival was negatively affected by the following factors: age > 60 years, poor-risk stratification, BM blast cell count >= 60%, and D-dimer >= 1 mu g/mL. Multivariate analysis showed that only age > 60 years (P < 0.001), BM blast cell counts >= 60% (P = 0.001) and D-dimer values >1 mu g/mL (P = 0.014) were independent adverse prognostic factors. Conclusions: D-dimer >= 1 mu g/mL is related to high tumor burden and can be considered as an independent prognostic factor in patients with de novo non-M3 AML.