Purpose <p>Esophagectomy for esophageal cancer involves high morbimortality when anastomotic leakage occurs. Optimal perfusion of the gastric tube can be assessed by indocyanine green fluorescence-angiography (ICG-FA). We evaluated whether locating the anastomosis in a zone enhanced within 60&#xa0;s after ICG-FA injection reduced severe anastomotic leakage (Stage 2 or 3) within 30&#xa0;days after esophagectomy.</p> Methods <p>ICG-FA was assessed in 69 patients and compared to 122 control patients undergoing minimally invasive Ivor Lewis esophagectomy. Whenever possible, the anastomosis was placed on gastric tissue enhanced within 60&#xa0;s after ICG-FA injection, with resection of the gastric tip if needed.</p> Results <p>Severe anastomotic leakage occurred in 8.4% of cases, with 6 cases of anastomotic leakage (8.7%) in the ICG-FA group and 10 (8.2%) in the non-ICG-FA group (<i>p</i> = 1.000). There was no difference in postoperative outcomes between both groups, the main complications being pulmonary. ICG-FA enhancement level at 60&#xa0;s was below the gastric tip in 33.8% of cases, with lowering of the anastomotic site in 18% of cases and resection of the gastric tip in 23% of cases. Overall, use of ICG-FA changed the surgical management in 29.9% of patients, with 2 patients presenting with anastomotic leakage.</p> Conclusion <p>Our results were not statistically significant, possibly due to a lack of power. There was no trend indicating a decrease in anastomotic leakage using our ICG-FA method, therefore other studies must help determine an optimal quantitative ICG-FA method to reduce postoperative morbidity after esophagectomy.</p>