Multimorbidity is frequent and represents a significant burden for patients and healthcare systems. However, there are limited data on the most common combinations of comorbidities in multimorbid patients. We aimed to describe and quantify the most common combinations of comorbidities in multimorbid medical inpatients. We used a large retrospective cohort of adults discharged from the medical department of 11 hospitals across 3 countries (USA, Switzerland, and Israel) between 2010 and 2011. Diseases were classified into acute versus chronic. Chronic diseases were grouped into clinically meaningful categories of comorbidities. We identified the most prevalent combinations of comorbidities and compared the observed and expected prevalence of the combinations. We assessed the distribution of acute and chronic diseases and the median number of body systems in relationship to the total number of diseases. Eighty-six percent (n = 126,828/147,806) of the patients were multimorbid (≥ 2 chronic diseases), with a median of five chronic diseases; 13% of the patients had ≥ 10 chronic diseases. Among the most frequent combinations of comorbidities, the most prevalent comorbidity was chronic heart disease. Other high prevalent comorbidities included mood disorders, arthropathy and arthritis, and esophageal disorders. The ratio of chronic versus acute diseases was approximately 2:1. Multimorbidity affected almost 90% of patients, with a median of five chronic diseases. Over 10% had ≥ 10 chronic diseases. This identification and quantification of frequent combinations of comorbidities among multimorbid medical inpatients may increase awareness of what should be taken into account when treating such patients, a growth in the need for special care considerations.