Abstract Background Thrombomodulin (TM) is a surface glycoprotein and expressed in many cancers. The aim of the present study was to detect the expression levels of TM in plasma and urine of bladder cancer patients and to compare these levels to the clinicopathological data of the patients as well as the ploidy status of their exfoliated urinary cells. We studied the levels of TM in plasma and urine samples of 57 bladder cancer patients and 10 controls using the (ELISA) assay and compared the results to the ploidy status of the cells taken from the patents urine samples as well as their clinicopathological profile. Results Urinary TM was significantly down regulated while plasma TM was significantly up regulated in bladder cancer patients. Plasma TM was significantly higher in SCC than TCC patients. The sensitivity and specificity of urinary TM were 90% and 86%, respectively. While the sensitivity and specificity of plasma TM were 76% and 80%, respectively. Conclusion Urinary TM is significantly down regulated, while plasma TM is significantly up regulated in bladder cancer as compared to the control group. Urinary TM has superior sensitivity and specificity over plasma TM. Urinary TM could be used as a predictive marker in bladder cancer. Further studies are needed to detect the prognosis significance of thrombomodulin in schistosomiasis associated bladder cancer.