Background: Anastomotic leak after esophagectomy carries important short- and long-term sequelae. The authors conducted a systematic review and meta-analysis to determine its association with surgical volume. Materials and methods: A systematic literature review was performed to identify all studies reporting on anastomotic leak after esophagectomy. Studies with less than 100 cases were excluded. The primary outcome was postesophagectomy anastomotic leak, while secondary outcomes were operative mortality overall and after anastomotic leak. Pooled event rates (PER) were calculated, and the association with annual esophagectomy volume by center was investigated. Results: Of the 3932 retrieved articles, 472 were included (n=177 566 patients). The PER of anastomotic leak was 8.91% [95% CI=8.32; 9.53%]. The PER of early mortality overall and after an anastomotic leak was 2.49% [95% CI=2.27; 2.74] and 11.39% [95% CI=9.66; 13.39], respectively. Centers with less than 37 annual esophagectomies had a higher leak rate compared to those with greater than or equal to 37 annual esophagectomies (9.58% vs. 8.34%; P=0.040). On meta-regression, surgical volume was inversely associated with the PER of esophageal leak and of early mortality. Conclusions: The frequency of anastomotic leaks after esophagectomy, perioperative, and leak associated mortality are inversely associated with esophagectomy volume.