The association between weight and blood pressure is well established, especially the paradigm of obesity-related hypertension. The relationship between diffuse autonomic dysfunction and orthostatic hypotension in patients with long-term diabetes mellitus is also well known. We report on a 57-year-old morbidly obese male with a long medical history of hypertension, myocardial infarction, type 2 diabetes mellitus, and hypothyroidism. After a loss of 147 pounds (representing a percent excess weight loss of 76%) within 6 months after gastric bypass surgery, the patient developed worsening orthostatic hypotension and near-syncopal episodes requiring medication. The subsequent diagnosis and treatment, as well as a literature review, are presented.