Abstract Introduction Anastomotic defect after esophagectomy can lead to severe complications with need for surgical or endoscopic intervention. Early detection enables early treatment and can limit the consequences of the anastomotic defect. As of today, there are limited methods to predict anastomotic defect. In this study we have used microdialysis to measure local metabolism at the intrathoracic anastomosis. Feasibility and possible diagnostic use were investigated. Methods Sixty patients planned for Ivor Lewis esophagectomy were enrolled. After construction of the anastomosis, surface microdialysis probes were attached to the outer surface of the esophageal remnant and the gastric conduit in close vicinity of the anastomosis and left in place for seven postoperative days. Continuous sampling of local tissue concentrations of metabolic substances (glucose, lactate, pyruvate) was performed postoperatively. Outcome, defined as anastomotic defect or not according to ECCG (Esophagectomy Complications Consensus Group) definitions, was recorded at discharge or at first postoperative follow up. Difference in concentrations of metabolic substances were analysed retrospectively between the two groups by means of artificial neural network technique. Results Surface micodialysis probes can be attached and removed from the gastric tube reconstruction without any adverse events. Deviating metabolite concentrations on POD 1 were associated with later development of anastomotic defect. In subjects who developed anastomotic defects, no difference in metabolic concentrations between the esophageal and the gastric probe was recorded. The technical failure rate of the microdialysis probes/procedure was high. Discussion Surface microdialysis can be used in a clinical setting after Ivor Lewis esophagectomy. Deviation in local tissue metabolism on POD 1 seems to be associated with development of anastomotic defects. Further development of microdialysis probes and procedure is required to reduce technical failure.