Background: Sp, or severe muscle wasting, has been implicated as an important prognostic factor in cancer pts. We assessed the association between body composition changes and outcomes in pts with esophageal cancer undergoing tri-modality therapy. Methods: Following IRB approval, we reviewed all pts who underwent chemoradiation followed by esophagectomy at an NCI-designated cancer center from 2000-2013. Pts who underwent CT assessment pre- and post-neoadjuvant chemoradiation were included in the analysis. Sp was defined as a lumbar skeletal muscle area/height of 55.4 cm²/m² for males and 38.9 cm²/m²for females. Fat mass (FM), fat-free mass (FFM), subcutaneous fat to muscle ratio (SFMR), and visceral to subcutaneous adipose tissue ratio (VSATR) were also derived using CT-based measures. Changes in the above parameters and Sp were correlated to post-operative (post-op) complications (cx), treatment (tx) response, disease free survival (DFS), and overall survival (OS). Analysis was performed using non-parametric Wilcoxon and Kruskal-Wallis tests, and Kaplan-Meier curves with log-rank tests. Results: A total of 48 pts met the inclusion criteria; the median age was 62 (range 42-80) with a median follow up of 28 months (range 4-103). Most pts had T3 (85%), N1 (70%), or M0/M1a disease (92%). Ten pts (21%) had Sp at the initiation of tx, with 9 of these remaining Sp post-tx, and 1 patient developing Sp. Post-tx Sp was associated with an increased rate of post-op mortality (p=0.03). Three of the 10 patients with Sp died post-op versus 1/36 in the non-Sp group. Post-tx Sp was associated with a decreased rate of post-op strictures (p = 0.04). Thirteen of the 36 pts in the non-Sp group developed strictures versus none in the Sp group. There was a significant change in all other measures pre vs. post-tx; FM (-4.3 kg/m², p<0.01), FFM (-5.0 kg/m², p<0.01), SFMR (-0.1, p=0.04), and VSATR (-0.02, p<0.01). None of these were correlated with post-op cx, tx response, DFS, or OS. Conclusions: Post-tx Sp was associated with an increased incidence of post-op mortality but a lower rate of strictures. Our study was limited by sample size, and further studies should examine the relationship between Sp and peri-operative outcomes.