D-dimer plasma levels were evaluated to determine whether they are altered by radiation. D-dimer levels were measured in radiation oncology patients, who were diagnosed with prostate, breast or lung cancer, or leukemia, as well as in healthy subjects serving as controls. Blood samples from radiotherapy patients were taken at three different time points: pre-, on- and post-radiotherapy. For the patients, considered together, differences between the D-dimer levels at these three time points compared to controls were statistically significant. Compared to the pre-radiotherapy measurements, radiation exposure was associated with a significant increase in the D-dimer levels at the on- and post-radiotherapy time points. At the post-radiotherapy time point, D-dimer levels in the patients were not significantly reduced compared to the on-radiotherapy levels, indicating that the risk for developing disseminated intravascular coagulation (DIC) may be increased in some radiation oncology patients. Of particular concern are the post-radiotherapy results observed for the D-dimer levels in the leukemia patients, in which the average fold increase in the D-dimer levels was 5.43 (compared to the pre-radiotherapy levels). These results suggest that leukemia patients might benefit from frequent assessment of their D-dimer levels after their total-body irradiation-conditioning regimen to detect early signs of DIC development. It is hoped that the results described here will lead to heightened awareness in the radiation oncology community that the risk of DIC development is greatly increased in some of these patients.