323 Background: Adenocarcinoma and squamous cell carcinoma of the esophagus have distinct outcomes, treatment strategies, and response profiles to therapy. Adenosquamous carcinoma (ASC) is thought to behave more aggressively than each of its counterparts. Our aim was to determine if ASC is best managed as adenocarcinoma or squamous cell carcinoma. Methods: The National Cancer Database (2004-15) was queried for patients with non-metastatic, esophageal ASC. Analysis was stratified by clinical node negative (cN0) or node positive (cN1-3) according to AJCC 8th edition. Treatment types were categorized into chemoradiation alone, surgery alone, or preoperative chemoradiation followed by surgery. Primary outcome was overall survival (OS). Results: Among 352 pts, median age was 67 yrs, 80% were male (n = 281). Median f/u was 46 mos. 43% were cN0 (n = 151), 57% were cN1-3 (n = 201). 55% had chemoradiation alone (n = 194), 15% had surgery alone (n = 53) and 30% had preoperative chemoradiation (n = 105). Of pts who had preoperative chemoradiation, 20% had pathologic complete response (n = 17). For either cN0 or cN1-3, Charlson-Deyo Comorbidity Index did not differ among the treatment groups (all p > 0.05). On KM analysis for cN0 disease, treatment with surgery alone had a comparable 5-yr OS to preoperative chemoradiation (47 vs 34% p = 0.5) and each had improved 5-yr OS compared to chemoradiation alone (30%; p = 0.02; p = 0.06). On UV analysis for patients with cN0 disease, clinical T-stage was not associated with 5-yr OS. For patients with cN1-3 disease, however, preoperative chemoradiation was associated with improved 5-yr OS when compared to chemoradiation alone or surgery alone (27 vs 19 vs 0% p < 0.001). This persisted even when accounting for age and clinical T-stage (HR 0.45 p < 0.001). Conclusions: Esophageal adenosquamous carcinoma behaves more like adenocarcinoma both in response to chemoradiation and survival outcomes based on the treatment modality. The complete response rate to chemoradiation is only 20% unlike what has been shown for squamous cell carcinoma, where chemoradiation is an acceptable definitive therapy. Esophageal adenosquamous carcinoma should be managed like adenocarcinoma and not squamous cell carcinoma.