Objectives: Hypothyroidism is usually detected in an outpatient setting, but might be diagnosed during hospitalization. The prevalent symptoms are not fully defined. This study aimed to determine the clinical characteristics of in-patients with overt hypothyroidism. Methods: The medical records of 23 inpatients (16F/7M, age 61.5 ± 21.8 years), who had 29 admissions with a primary diagnosis of hypothyroidism from January 1997 to December 2007 were retrospectively reviewed. They comprised 0.01% of all adult medical admissions during the study. Results: Fifty-five percent had a pre-admission diagnosis of hypothyroidism, 10% were nursing home residents and 38% had cognitive decline. Sixtynine percent presented with multiple complaints, mostly weakness and constipation, reported by 89% and 68%, respectively. Thyrotropin level was 74.3 ± 53.5 mIU/L (normal 0.23 - 4) and free thyroxine was 0.43 ± 0.29 ng/dL (normal 0.8 - 2). Elevated creatinine phosphokinase, anemia (hemoglobin < 12 g/dL) and hyponatremia (sodium < 135 mEq/L) were present in 89%, 62%, and 13%, respectively. Conclusions: Overt hypothyroidism during hospitalization occurs infrequently and mostly in patients with previously diagnosed hypothyroidism. Clinical manifestations include multiple non-specific symptoms, mainly weakness and constipation, while typical “hypothyroid” symptoms such as cold intolerance and weight gain are often overlooked. A high index of suspicion is needed to detect hypothyroidism in the hospital setting.