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Aim The aim of this study was to assess whether a preoperative HH≥3cm had an impact on histopathologic tumor response after neoadjuvant treatment, as well as on overall and disease-free survival. Background & Methods Hiatal hernia (HH) and long-term gastroesophageal reflux are known risk factors for esophageal cancer. Previous data suggest a negative impact of large hiatal hernias on survival after esophagectomy, as well as an increased toxicity after neoadjuvant treatment (1), although evidence remains scarce and the mechanism is not fully elucidated. All consecutive patients who underwent surgical esophagectomy for adenocarcinoma or squamous cell cancer of the esophagus and gastro-esophageal junction from 2012-2018 were assessed. Baseline oesogastroduodenoscopy reports and CT-scan images were retrospectively reviewed to identify the presence of a HH of ≥3cm (2). Response to neoadjuvant treatment as assessed by the Mandard score (3), postoperative outcomes and survival were compared between HH and non-HH patients (defined as HH<3cm or no HH at all). Categorical variables were compared with the x2 or Fisher’s test, whereas continuous ones with the Mann-Whitney-U test. The Kaplan-Meier method and log-rank test were used for survival analyses. Results Among the 174 included patients, 44 (25.3%) had a HH≥3cm upon diagnosis. HH patients compared to the non-HH had significantly more Barrett’s metaplasia (52.3% vs 20%, p<0.001), although no differences in baseline stage were observed. HH patients presented a worse response to neoadjuvant treatment compared to non-HH patients (TRG 4-5 in 40.5% vs 21.3%, p=0.033). Among HH patients, perioperative chemotherapy compared to radiochemotherapy showed a trend to higher complete response rates (TRG 1 in 25% vs 11.5%, p=0.059). In the radiochemotherapy subgroup (n=112), HH patients had worse complete response rates than non-HH patients (TRG 1 in 11.5% vs 26.7% respectively, p=0.050). However, no differences in overall or disease-free survival were observed between HH and non-HH patients in the whole cohort or in subgroup analyses. Conclusion A HH≥3cm is frequently encountered in esophageal cancer patients. The presence of HH was associated with worse response to neoadjuvant treatment, especially radiochemotherapy. However, the presence HH did not have an impact on long-term survival and recurrence.