OBJECTIVE: Renin-angiotensin aldosterone system (RAAS) signaling affects tumorigenesis and treatment susceptibility of various cancers. We investigate the impact of angiotensin-system inhibitors (ASI) on survival in patients treated with locally advanced esophageal adenocarcinoma (EAC). METHODS: EAC patients receiving trimodal therapy from 2002 to 2017 at a single institution were abstracted. Primary outcomes were overall survival (OS) and disease-free survival (DFS), analyzed with the Kaplan-Meier method, Cox regression, and propensity score-matched analysis. Secondary outcomes included pathologic complete response and tumor regression grade. RESULTS: 375 patients with EAC were included. 92 patients (25%) were ASI users (ASI CONCLUSION: RAAS inhibition during esophageal cancer treatment is associated with improved outcomes. Our study suggests that ASIs may provide additional survival benefits in the multi-modality treatment of EAC.