Background: For distal rectal tumors, abdominoperineal resection (APR) may achieve a complete resection; however is associated with significant morbidity. Full thickness local excision (FTLE) via transanal endoscopic microsurgery (TEM) may provide disease control with fewer complications. Additionally, Intensity Modulated Radiation Therapy (IMRT) may minimize toxicity by limiting small bowel exposure to radiation. We report on 14 years of prospective data from Lankenau Medical Center for distal rectal cancer pts treated with neoadjuvant chemotherapy and high dose IMRT followed by FTLE via TEM. Methods: From 2002 to 2016, 44 pts were treated for cT1(n = 4), cT2 (n = 24), cT3 (n = 16), N0, M0 distal rectal cancer using IMRT at 5580 cGy along with concurrent 5FU-based chemotherapy, followed by FTLE. Local recurrence (LR), disease free survival (DFS) and overall survival (OS) was reported using Kaplan-Meier survival analysis. Results: At the time of FTLE complete pathological response was achieved in 18 pts, good response in 25 pts, and 1 pt with poor response. Median time to follow-up is 58 months. 3 of 44 pts (6.8%) had isolated local recurrence, all achieving local control with surgical salvage. Mean DFS is 10.68 years (95% CI 8.77 to 12.60). Mean OS is 11.78 years (95% CI 9.99 to 12.58). 34 pts (77%) are currently alive with NED. 6 pts developed metastatic disease, 5 of whom died, and one who was surgically salvaged. 5 pts died from causes outside of their malignancy. In adjusted analysis, DFS was strongly associated with pathologic response to chemoradiotherapy (p = 0.025). Post-operative Grade I-II complications noted in 17 pts, all managed with conservative measures; Grade III occurred in 2 pts. No pts required a diverting colostomy. Conclusions: Neoadjuvant high dose IMRT and chemotherapy followed by FTLE to treat distal rectal cancers is well tolerated and effective. Local excision surgery may provide excellent tumor control and improved quality of life in appropriately selected pts. A randomized clinical trial is needed to compare it to standard surgery. Also a dose escalation study with IMRT may allow for improvement in pathologic response without increasing toxicity.