Our institution has previously demonstrated a survival advantage conferred by preoperative neoadjuvant therapy for locally advanced rectal cancers. We now report our results using transanal excision as definitive surgical therapy in a selected group of patients who experienced significant downstaging of T3 rectal cancers after neoadjuvant therapy. Seventy-four patients diagnosed with locally advanced (T3) rectal cancers were treated with neoadjuvant chemoradiotherapy. After neoadjuvant therapy, 11 (14.9%) patients who had significant downstaging of their tumors were selected to undergo transanal excision of their residual rectal cancers. Intraoperative cryostat evaluation was used to confirm negative margin status, and all patients were subsequently followed with routine endoscopy, transrectal ultrasonography, and digital rectal examinations. Tumors were located between 1 cm and 7 cm from the anal verge (mean 4.3 +/- 0.6 cm), and were located in lateral, anterior, and posterior positions. Mean followup was 55.2 +/- 8.9 months (median 47.9 months). Imaging studies using CT, MRI, transrectal ultrasonography, or combination demonstrated suspicious lymph nodes in three patients. After neoadjuvant therapy, these lymph nodes were no longer demonstrated in two patients. There were no local recurrences, nodal metastases, or operative mortalities. One patient (9%) developed distant metastases (pulmonary nodules), and remains alive 30 months after transanal excision. One patient (9%) experienced sphincter laxity, which was successfully repaired, and is now asymptomatic. One patient (9%) developed postoperative urgency that resolved spontaneously. In patients who have initial bulky (T3) lesions, and experience significant downstaging after neoadjuvant chemoradiotherapy, transanal excision appears to be a safe and effective treatment, preserving sphincter function and avoiding laparotomy.