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Introduction: The use of neoadjuvant chemoradiation (NCR) is widely regarded as the standard of care for patients with locally advanced rectal cancer (RC). For colon cancer, the pathologic nodal status is a clear prognostic indicator. For RC treated with NCR, due to accuracy rates of pre-treatment nodal staging and potential downstaging of nodes, the prognostic significance of pathologic nodal status is less clear. Methods: From 1998-2008, a total of 174 patients were identified as having undergone NCR and radical resection for RC. Clinicopathologic and survival data were reviewed. Univariate analyses and multivariate analyses were performed. For analyses, patients were grouped into 4 nodal categories (uN0-pN0, uN0-pN+, uN+-pN+ and uN+-pN0). Results: Our study population consisted of 104 men and 70 women with a median age of 60 years (29-85 yrs) and a median follow up of 31 months (1-116 mo). Following NCR, 140 patients underwent low anterior resection and 34, abdominoperineal resection (APR) with 90% of patients receiving adjuvant chemotherapy. On univariate analysis, nodal category (p=0.003), R1 resection (p=0.03), and APR (p=0.04) were found to negatively influence DFS. With respect to nodal category, DFS was significantly impacted by the final pN status but not by pre-operative uN status (Figure 1). Nodal category approached significance (p=0.05) as a predictor of OS. However, patients with nodal downstaging (uN1-pN0) had a significant survival advantage compared to patients with nodal progression (uN0-pN+) (p=0.03). On multivariate analyses, pathologic nodal positivity (p=0.03; HR 2.84; CI 1.11-7.24) was an independent predictor for DFS. Conclusions: For patients with rectal cancer treated by NCR, pathologic rather than pre-operative nodal status represents an independent predictor of DFS. This may have important potential implications for the application of adjuvant therapy.