OBJECTIVE: Tumor blood vessels are tortuous and dilated, contributing to the aberrant tumor microenvironment. CD93 is a newly reported transmembrane receptor, mainly expressed in tumor endothelial cells, that has demonstrated prognostic value in some cancer types. However, the role of CD93 in the vasculature of colorectal cancer (CRC) tissues and its prognostic significance remain unknown. It is therefore necessary to explore the effect of CD93 in patients with CRC. METHOD: We detected the expression of CD93 in human CRC tissues using immunohistochemistry. We then examined the correlation between CD93 expression and clinicopathological factors in cancer tissues from 134 patients with CRC. RESULT: CD93 expression levels were higher in CRC vessels than in vessels in adjacent normal tissues. Upregulation of CD93 was associated with tumor site and microsatellite instability. CD93 protein expression was positively related to macrophage infiltration in CRC. High expression of CD93 may indicate normalization of the tumor vasculature and was associated with better overall survival. CONCLUSION: CD93 was highly expressed in CRC vessels and correlated with infiltration of immune cells. Our findings reveal that vascular normalization and patient prognosis can be predicted by detecting CD93 expression in CRC tumor tissues.