Esophagogastric anastomotic leaks are the most feared surgical complications following resection of esophageal cancers. We aimed to develop a therapeutic algorithm for this complication characterized by high morbidity and mortality using our 20 years of experience and the published literature. A total of 354 patients who had undergone an esophagectomy and esophagogastric anastomosis due to esophageal carcinoma were evaluated retrospectively. The incidence for anastomotic leak was 15.5% (n = 90) in the cervical region and 4.2% (n = 264) in the thoracic region (mean: 7.1%). Cervical anastomotic leaks were detected after a mean period of 7.2 days following the procedure. Fourteen patients with cervical leaks were treated conservatively. Four out of 14 patients (28.6%) died due to sepsis and multi-organ failure related to fistula. Thoracic anastomotic leaks were detected after a mean period of 4.7 days following the procedure. Emergency reoperation, resection and reconstruction procedures were performed in one patient. Self-expanding metallic coated stents were placed at the anastomosis region in two patients. A more conservative approach was employed in other patients with thoracic anastomotic leaks. Six of them (46.2%) died due to fistula. General mortality rate was 37.0%, and the duration of hospitalization was 40.0 days for patients with anastomotic leaks. Cervical anastomotic leaks are more common than thoracic anastomotic leaks, but most of them are successfully treated with conservative approaches. Thoracic anastomotic leaks that in the past were related to high mortality rates despite conservative or surgical procedures might be successfully treated nowadays with the use of self-expanding metallic coated stents.