Purpose: The role of EUS after endoscopic polypectomy of high risk rectal lesions is unclear. Our purpose is to review the yield of EUS after polypectomy of high risk rectal lesions. Methods: Patients referred from 10/02-10/09 to our hospital for EUS following endoscopic polypectomy of high risk rectal lesions were included. High risk lesion: tubulovillous adenoma (TVA), tubular adenoma with high grade dysplasia (TA-HGD), carcinoid or carcinoma. Staging EUS for: 1) residual lesion in the rectal wall or; 2) lymph node (LN) involvement. Results stratified in 2 groups by presence or absence of cancer (CA). Incremental yield of EUS defined as: 1) residual neoplasia not seen on white light endoscopy (WLE) and biopsy (WLE/BX) and; 2) abnormal perirectal LNs. The sensitivity and specificity for detection of residual pathology was calculated for WLE/BX and EUS using results from biopsies, later surgery and/or follow up when possible. Results: 70 patients (mean age 64 yrs, 39% female) with a final CA (n=38) and non-CA (n=32) diagnosis were enrolled. Initial polypectomy pathology: adenocarcinoma in 36 (57%), TVA in 17 (24%), TA-HGD in 12 (17%), carcinoid in 3 (4%) and other in 2 (3%). EUS (mean 35±24 days after endoscopy): wall thickness in 45 (64%), residual mass in 14 (20%), normal in 11 (16%). WLE during EUS: ulcer in 22 (31%), scar in 21 (30%), polyp/mass in 19 (27%), normal in 8 (12%). Pinch biopsies during EUS in 21 (55%) CA and 20 (62%) non-CA patients: residual CA in 8 (21%); TA-HGD in 6 (9%) and CA in 1 (3%) non-CA. EUS of the rectal wall did not identify a residual mass that would have been missed by WLE/BX alone. A LN was seen in 5 (13%) CA patients; EUS-FNA confirmed CA in 1. No abnormal-appearing LNs were seen in the non-CA group. Follow-up (median 40 mos.; range: 1-93) in the CA patients (available in 55% [21/38]) included: transanal excision in six, laparotomy in four, chemoradiation in three and repeat endoscopy in eight. Of the 8 patients who underwent endoscopy alone without further treatment, no local recurrence occurred during a median follow-up of 40 mos (range 3-78). Follow-up (median 33 mos; range: 1-93) in the non-CA group (available in 62% [20/32] included: transanal resection in two, laparotomy in one and surveillance alone in 17. In the surveillance group (median follow-up: 45 months (range: 6-72), two recurrent adenomas were seen 8 and 17 months after EUS. For detection of residual lesions, the sensitivity/specificity of WLE/BX and EUS were 87%/86% and 60%/86%, respectively. Conclusion: Following endoscopic polypectomy of high risk rectal lesions, the incremental yield of EUS compared to WLE/BX for evaluation of residual intramural disease appears limited, particularly in benign lesions.