Background: The main objective of this study was to determine whether there was a correlation in the levels of various angiogenesis-related factors between the tumor drainage and peripheral venous blood and whether appraisal of angiogenic factor levels in the tumor drainage venous blood could provide better prognostic information for patients with colorectal cancer than assessment of the peripheral venous blood. Methods: Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and enclostatin were measured and compared in both tumor drainage and peripheral venous blood from 52 patients with colorectal cancer. Plasma levels of angiogenesis-related factors were also correlated with tumor stage and clinical outcomes. Results: The plasma endostatin level was significantly higher ill peripheral blood than in tumor drainage venous blood (P < .001). The plasma VEGF level was significantly correlated with plasma endostatin levels (P = .028 in tumor drainage venous blood and P = .002 in peripheral venous blood). Ill both tumor drainage and peripheral venous blood, the VEGF level (but not the basic fibroblast growth factor or enclostatin level) was significantly correlated with tumor stage and disease recurrence. However, in multivariate analysis, only plasma VEGF level in tumor drainage venous blood remained an independent predictor of disease recurrence. Conclusions: The plasma VEGF level in tumor drainage venous blood provided better prognostic information than that in peripheral venous blood. The plasma enclostatin level was paradoxically significantly higher in peripheral than in tumor drainage blood, and this strongly suggests additional sources of enclostatin in peripheral blood.