Many studies have established the usefulness of serum carcinoembryonic antigen (CEA) oriented serial monitoring for predicting recurrence and prognosis; however, few studies have so far investigated serum CEA-negative recurrence. The aim of this study was to elucidate the nature of CEA-negative recurrence regarding tumor angiogenesis. Fifty-seven patients with T3/T4 rectal cancer were divided into the two groups according to the serum CEA status. Angiogenesis was defined as the intratumoral vessel count by immunohistochemical staining using CD31. The CD31 count was significantly higher in the recurrent patients in both groups and the ratio of nodal involvement was significantly higher in the recurrent patients of the CEA-negative group. Local recurrence mainly developed in the CEA-negative group; however, the CD31 count did not predict the sites of recurrence nor the relapse period in the both groups. A multivariate analysis showed a high CD31 count >26) to be a prognostic factor not only for recurrence but also for survival (P = 0.001, 0.043, respectively). These results suggest that a high degree of tumor angiogenesis in sections of T3/T4 rectal cancer may therefore be an important predictor for CEA-negative recurrence.