Orthostatic hypotension is associated with significant morbidity and mortality in elderly patients. In orthostatic hypotension caused by central and peripheral nervous system disorders (neurogenic orthostatic hypotension), the release of catecholamine in the standing posture is insufficient to compensate adequately for decreased venous return to the heart. Primary autonomic failure exhibits, often, supine hypertension, that can be worsened by pressor agents, such as midodrine, used to prevent syncope episodes. Salt-retaining steroid fludrocortisone, also, used to treat orthostatic hypotension, increases blood pressure both in supine and in standing position. We describe 3 patients with neurogenic orthostatic hypotension caused by pure autonomic failure. They complained of several syncope episodes. On examination, orthostatic hypotension and supine hypertension were detected in the absence of pharmacological therapy. All the patients presented hypertensive organ disease. Fludrocortisone acetate was started in one patient, and short-acting vasopressor agents during the day and dihydropyridine-calcium antagonist during the night in the other two. During the follow-up a transient ischemic attack occurred in the patient treated with fludrocortisone. When fludrocortisone was titrated down and short-acting antihypertensive drugs were started, the patient did not complain of any symptoms. Supine hypertension is part of pure autonomic failure, and short-acting antihypertensive agents should be associated with vasopressor agents to prevent hypertensive target organ disease.