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The aim of the study was to evaluate laser-assisted fluorescent-dye angiography (LAA) to assess perfusion in the gastric graft and to correlate perfusion with subsequent anastomotic leak.Anastomotic leaks are a major source of morbidity after esophagectomy with gastric pull-up (GPU). In large part, they occur as a consequence of poor perfusion in the gastric graft.Real-time intraoperative perfusion was assessed using LAA before bringing the graft up through the mediastinum. When there was a transition from rapid and bright to slow and less robust perfusion, this site was marked with a suture. The location of the anastomosis relative to the suture was noted and the outcome of the anastomosis ascertained by retrospective record review.Intraoperative LAA was used to assess graft perfusion in 150 consecutive patients undergoing esophagectomy with planned GPU reconstruction. An esophagogastric anastomosis was performed in 144 patients. A leak was found in 24 patients (16.7%) and were significantly less likely when the anastomosis was placed in an area of good perfusion compared with when the anastomosis was placed in an area of less robust perfusion by LAA (2% vs 45%, P < 0.0001). By multivariate analysis perfusion at the site of the anastomosis was the only significant factor associated with a leak.Intraoperative real-time assessment of perfusion with LAA correlated with the likelihood of an anastomotic leak and confirmed the critical relationship between good perfusion and anastomotic healing. The use of LAA may contribute to reduced anastomotic morbidity.