To find a more appropriate alternative to D-dimer cutoff value for the diagnosis of deep vein thrombosis (DVT) in cancer patients. A total of 711 cancer patients with symptoms suspicious of DVT were included in the study. D-dimer levels were assessed using ELISA. All patients were subjected to imaging procedures. Among 711 patients with cancer, 466 (65.5%) were females and 245 (34.5%) were males, with an average age of 57.3 ± 13.23 years. The mean age in the DVT group was significantly higher than in the non-DVT group (P<0.05). The D-dimer levels of the DVT group were significantly higher than those of the non-DVT group (P<0.05). The incidence rate of DVT varied significantly according to cancer type (P<0.05). Increasing age and lung cancer were significantly correlated with D-dimer levels (P<0.05), and a one-year increase in age was associated with a 14.28 ng/ml increase in the D-dimer value. The optimal cutoff point for D-dimer was found to be 981 ng/ml, with a sensitivity of 86.4%, specificity of 79.4%, and accuracy of 82.6%. If the D-dimer cutoff point was set to 981 ng/ml, the specificity would increase from 61.8% to 85.5% without loss of sensitivity in patients aged 40 years or younger. In patients aged more than 40 years, the new cutoff almost doubled the specificity with slightly reduced sensitivity. In cancer patients, a new cutoff value of 981 ng/ml effectively improved the exclusion of DVT, especially for patients aged more than 40 years.