Objective To evaluate the safety and efficacy of 125I radioactive seeds implantation combined with postoperative chemotherapy as a treatment option for thoracic advanced esophageal squamous cell carcinoma(ESCC). Methods A prospective cohort study was carried out between 2000and 2005. According to preoperative CT staging criteria,298 patients in phase Ⅱ-Ⅲ of ESCC, who had were admitted to Oncology Center Surgery of Nanjing First Hospital Affiliated to Nanjing Medical University and Thoracic Surgery of YanCheng Oncology Hospital, were randomly divided into three groups: intraoperative 125I seeds implantation combined with postoperative chemotherapy (group A, 98cases), postoperative chemoradiotherapy (group B, 100 cases) and surgery alone (group C, 100cases). All patients received radical resection of esophageal cancer. According to pTNM staging criteria after operation, 233 patients in phase Ⅱb-Ⅲ of ESCC were finally enrolled in the study (78 in group A, 75 in group B, and 80 in group C). With 0. 5 m Ci of single seed, total activity of 5-11 mCi and matched peripheral dose in 60-70 Gy, 10-22 125I seeds were implanted into the target of patients in group A under direct vision in accordance with treatment planning system. The validation and quality assessment of radioactive seeds were demonstrated according to CT scan or X-ray imaging. The postoperative complications were observed. The local recurrence of the cancer was demonstrated using CT scan. The survival rate of patients was followed up for 1-,3-,5- and 10 years. Results The satisfied quality assessment of 125I seeds was observed. There was no displacement or loss of seed. The local recurrence in group A, B and C was 11. 5%, 13. 3% and 38. 8%, respectively, with statistical significance (P < 0. 05). There was no significant difference among three groups with respect to complications and 1-year survival (P>0. 05). However, the overall survival rate 3-, 5- and 10-years was 64.8%,37. 7% and 25. 1% in group A respectively; 63.3%, 36.9% and 24.9% in group Brespectively; 43. 6i%, 25.0%, and 12.6% in group C, respectively (all P<0. 05). The 3-,5- and 10-year progression free survival rates were 63.5 %, 37.4 % and 15.1% in group A respectively; 62.5 %,36.6% and 14. 4% in group B respectively; 42.5%, 25.6% and 6.2% in group C respectively (all P<0. 05). Conclusions It is a safe, effective and simple method for intraoperative 125I seeds implantation combined with postoperative chemotherapy in treatment of advanced ESCC, which may reduce the local recurrence and improve survival rates in patients with ESCC. Key words: Esophageal squamous cell carcinoma; Radioactive seed; 125I or 125I; Brachytherapy; Esophagectomy