Patients with hypopituitarism face excess mortality in the long-term outpatient setting. However, associations of pituitary dysfunction with outcomes in acutely hospitalized patients are lacking.To assess clinical outcomes of hospitalized patients with hypopituitarism with or without diabetes insipidus.In this population-based matched cohort study from 2012 to 2017, hospitalized adult patients with a history of hypopituitarism were 1:1 propensity-score matched with a general medical inpatient cohort.The primary outcome was in-hospital mortality. Secondary outcomes included all-cause readmission rates within 30 days and 1 year, ICU admission rates, and length of hospital stay.After matching, 6'764 cases were included in the study. In total, 3'382 patients had hypopituitarism and of those 807 (24%) suffered from diabetes insipidus. All-cause in-hospital mortality occurred in 198 (5.9%) of patients with hypopituitarism and in 164 (4.9%) of matched controls (OR 1.32, 95%CI, 1.06-1.65, P=0.013). Increased mortality was primarily observed in patients with diabetes insipidus (OR 3.69 [95%CI, 2.44-5.58], P<0.001). Patients with hypopituitarism had higher ICU admissions (OR 1.50 [95%CI, 1.30-1.74], P<0.001), and faced a 2.4-day prolonged length of hospitalization (95%CI, 1.94-2.95, P<0.001) compared to matched controls. Risk of 30-day (OR 1.31 [95%CI, 1.13-1.51], P<0.001) and 1-year readmission (OR 1.29 [95%CI, 1.17-1.42], P<0.001) was higher among patients with hypopituitarism as compared with medical controls.Patients with hypopituitarism are highly vulnerable once hospitalized for acute medical conditions with increased risk of mortality and adverse clinical outcomes. This was most pronounced among those with diabetes insipidus.