Background and purpose: Patients who are being admitted to a hospital due to diseases other than stroke may develop a stroke (in-hospital stroke; IHS). Methods: We enrolled 111 consecutive patients who developed IHS outside a neurology ward during a 5-year period at a single hospital. The frequency, characteristics, and outcomes for IHS patients were compared with patients who develop ischaemic stroke outside of the hospital (out-of-hospital stroke; OHS). Results: Forty-six percent of IHS occurred in the department of cardiology or cardiovascular surgery and 60% were associated with surgery or procedures. In comparison with the OHS patient group, the IHS patient group showed an increased frequency of cardiac disease, leukocytosis, and anemia. Cardioembolism, stroke of other determined etiologies, and an incomplete evaluation were more common in the IHS group, whereas large artery atherosclerosis was more frequent in the OHS group. The IHS group had up to a 10-fold higher mortality than the OHS group, with sepsis being the most common cause of death in the IHS group. Conclusions: IHS has distinct etiologies and stroke mechanisms from OHS. The prevention and management of infection could decrease mortality in IHS patients.