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Background: Ramucirumab is an anti-angiogenic drug that received Food and Drug Administration (FDA)-approvals for treatments of many cancers. Gastrointestinal fistulas and perforations are recognized side effects of anti-angiogenic therapies, however, there are very few reported cases of these conditions in patients managed with Ramucirumab. Here we report a case of a 46-year-old gentleman with a stage four gastroesophageal junction tumor, who developed multiple tracheoesophageal fistulas post ramucirumab containing regimen. To the best of our knowledge, this is the first case report that describes a serious uncommon complication of ramucirumab in a patient with a gastroesophageal junction tumor.