Diffuse idiopathic skeletal hyperostosis (DISH) has been associated with various metabolic disorders considered to be cardiovascular risk factors such as obesity, diabetes mellitus, hyperinsulinemia, and hyperlipidemia. To evaluate morbidity and mortality of hospitalized patients with DISH admitted to the department of medicine. One hundred patients from a cohort of 1020 consecutive patients, aged 45 years and more, admitted to the department of medicine were diagnosed as suffering from DISH. Another group of 100 patients, age- and gender matched, admitted without DISH, served as controls. Clinical and demographic characteristics, diagnoses on admission, previous chronic diseases, chronic medical therapy, laboratory tests, and the rates of in-hospital mortality and readmissions within 1 month of discharge were collected from the hospital database, for the two groups. Uncompensated or paroxysmal atrial fibrillation was more often encountered on admission in patients with DISH (p = 0.038). Patients with DISH were more likely to suffer from elevated body mass index, arterial hypertension, diabetes mellitus, and previous cerebral vascular accidents, although the differences did not reach statistical significance. However, significantly more patients had an electrocardiographic evidence of left ventricular hypertrophy (p = 0.03). The mortality rate was similar between the two groups. The lack of significant associations for cardiovascular risk factors such as diabetes mellitus, hypertension, and high BMI should be interpreted cautiously considering the characteristics of the control group. Identification of comorbid conditions and proper therapeutic interventions may prove useful in reducing the morbidity and mortality associated with this disorder.