OBJECTIVE To assess the feasibility, efficacy, and morbidity of (125)I seeds interstitial permanent implant as salvage therapy for re-recurrent rectal cancer. METHODS From September 2003 to October 2007, (125)I seeds implant procedures were performed under CT or ultrasound guidance for thirteen patients with locally re-recurrent rectal carcinoma. The minimal peripheral doses (MPD) of (125)I seeds implanted ranged from 120 to 160 Gy, with a median MPD of 140 Gy to total decay. Three patients also received two to four cycles of chemotherapy after seed implantation. RESULTS After a median follow-up of 10 months (range 3-45), the pain-free interval was 0-14 months with a median of 7 months (95% CI: 3-11 months). The response rate of pain relief was 46.2% (6/13). Local control was 3-14 months with a median of 7 months (95% CI: 3.5-10.5 months). The 1- and 2-year local control rates were 14.4% and 0%, respectively. Three (23.1%) patients died of local recurrence; seven (53.8%) patients died of local recurrence and metastases; one (7.7%) patient died of metastases. Two (15.4%) patients survived to follow-up. At the time of analysis, the median survival was 10 months (95% CI: 3.9-16.1 months). The 1- and 2-year actuarial overall survival rates were 46.2% and 11.5%, respectively. Two (15.4%) patients experienced a grade 4 toxic event. Seed migration to the pelvic wall was observed in one (7.7%) patient. There was no associated neuropathy. CONCLUSIONS (125)I seed implantation is feasible, effective, and safe as a salvage or palliative treatment for patients with re-recurrent rectal cancer.