Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. Endoscopic interventions that ablate Barrett's esophagus mucosa lead to replacement with a new squamous (neosquamous) mucosa, but it can be difficult to achieve complete ablation. Knowing whether cancer is less likely to develop in neosquamous mucosa or residual Barrett's esophagus after ablation is critical for determining the efficacy of treatment. This issue can be informed by assessing biomarkers that are associated with an increased risk of progression to adenocarcinoma. Although there are few postablation biomarker studies, evidence suggests that neosquamous mucosa may have a reduced risk of adenocarcinoma in patients who have been treated for dysplasia or cancer, but some patients who do not have complete eradication of nondysplastic Barrett's esophagus may still be at risk. Biomarkers could be used to optimize endoscopic surveillance strategies following ablation, but this needs to be assessed by clinical studies and economic modeling.