Valid biomarkers for a better prognostic prediction of the clinical course in esophageal adenocarcinoma (EAC) are still not implemented. Integrin alpha V (ITGAV), a transmembrane glycoprotein responsible for cell-to-matrix binding has been found to enhance tumor progression in several tumor entities. The expression pattern and biological role of ITGAV expression in esophageal adenocarcinoma (EAC) has not been analyzed so far. Aim of the study is to evaluate the expression level of ITGAV in a very large collective of EAC and its impact on individual patients´ prognosis. 585 patients with esophageal adenocarcinoma were analyzed immunohistochemically for ITGAV. The data was correlated with clinical, pathological and molecular data (TP53, HER2/neu, c-myc, GATA6, PIK3CA and KRAS). A total of 85 patients (14.3%) out of 585 analyzable tumors showed an ITGAV expression and intratumoral heterogeneity was low. ITGAV expression was correlated with a shortened overall-survival in the patients´ group that underwent primary surgery (p = 0.014) but not in the group of patients that received neoadjuvant treatment before surgery. No correlation between any of the analyzed molecular marker (mutations or amplifications) (TP53, HER2, c-myc, GATA6, PIK3CA and KRAS) and ITGAV expression could be observed. A multivariate cox-regression model was performed which showed tumor stage, lymph node metastasis and ITGAV expression as independent prognostic markers for overall-survival in the group of patients without neoadjuvant treatment. ITGAV expression is correlated with an impaired patient outcome in the group of patients without neoadjuvant therapy and serves as a prognostic factor in EAC.