To evaluate the aetiology and the diagnostic yield of the standardized diagnostic work-up based on European Society of Cardiology guidelines in the syncope unit. A total of 501 patients (191 men and 310 women), mean age 65 years (44–75 years), were prospectively evaluated. They underwent initial evaluation (history, physical evaluation, and a 12-lead electrocardiogram) and subsequently targeted tests that differed according to suspected aetiology. Initial evaluation resulted in diagnosis in 155 patients—reflex syncope (93), arrhythmogenic syncope (62), and pacemaker malfunction (7). In 22 patients with solitary syncope, a diagnostic algorithm was stopped after initial evaluation. In 139 patients with organic heart disease, cardiac syncope was found in 83 patients and reflex syncope in 30 patients. In 185 patients without organic heart disease, reflex syncope was diagnosed in 127 patients, cardiac syncope in 30 patients, and vascular syncope in 2 patients. Vasovagal syncope was the most common type of syncope (43%), followed by bradyarrhythmias (25%), tachyarrhythmias (9%), and orthostatic hypotension (5%). Aetiology of syncope remained unknown in 11% of patients. Diagnostic yield of specific examinations was as follows: head-up tilt 52%, implantable loop recorder 51%, electrophysiologic study 33%, initial evaluation 31%, EKG Holter 12%, orthostatic test 10%, transoesophageal stimulation 9%, carotid sinus massage 4%, and echocardiography 2%. Standardized diagnostic evaluation determined the aetiology of syncope in 89% of patients. Diagnostic yield of specific diagnostic procedures was different. Initial evaluation resulted in diagnosis in one-third of patients.