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Purpose Carcinoembryonic antigen (CEA) is a tumor marker for colorectal cancer (CRC) related to recurrence and prognosis. We examined the ability of the CEA level measured directly from a tumor drainage vein (dCEA) to predict the prognosis of CRC more accurately than those from a peripheral vein (pCEA). Methods Fifty-two patients who received curative resection for colon adenocarcinoma were enrolled. The patients were categorized into two groups according to normal pCEA (<5.9425 ng/mL, n=24) or elevated pCEA levels (≥5.9425 ng/mL, n=28). Blood was sampled at the time of surgery simultaneously from the tumor drainage vein and from the peripheral vein. Results The clinicopathologic variables showed no significant difference between the two groups. Patients with dCEA levels <20.192 ng/mL showed better disease-free (P=0.009) and overall survival (P=0.033) curves than those with dCEA levels ≥20.192 ng/mL. Elevated dCEA levels were a significant prognostic factor for overall survival and disease-free survival in Cox proportional hazard model analysis (hazard ratio [HR]=399; 95% confidence interval [CI], 16.4–9,747; P<0.001; HR=9.39, 95% CI, 1.29–68.006; P=0.026). In subgroup analysis, we compared the data of normal range of dCEA group and elevated dCEA group with normal pCEA; the overall survival rate of patients with normal dCEA was better and the disease-free survival rate was significantly better (P=0.003). Conclusion CEA levels from a tumor drainage vein can be used as more accurate prognostic markers than levels from a peripheral vein in patients with colon cancer.