BACKGROUND Fifty years after the inception of the cardiac intensive care unit (CICU), noncardiovascular illnesses have become more prevalent and may contribute to morbidity and mortality. OBJECTIVES The authors performed multivariate statistical analyses to determine the association of acute noncardiovascular illnesses with outcomes, including length of stay (LOS), mortality, and hospital readmission. METHODS We studied 1,042 admissions between October 12, 2013 and November 28, 2014 to the CICU at the University of Virginia Health System, a tertiary-care academic medical center. Through systematic inspection of individual charts, we identified primary and secondary diagnoses, vital sign measurements, length of stay (LOS), hospital readmissions, and mortality. RESULTS The most common primary diagnosis was acute coronary syndrome (25%), which consisted of both non-ST-segment elevation acute coronary syndrome (14%) and ST-segment elevation myocardial infarction (11%). Sepsis was the most frequent noncardiovascular primary diagnosis (5%), but it only occurred in 16% of all admissions. Acute kidney injury and acute respiratory failure each occurred in 30% of admissions. One-half of all admissions (n = 524; 50%) were marked by acute respiratory failure, acute kidney injury, or sepsis. Median LOS in the CICU and the hospital were 2 days (interquartile range [IQR]: 1 to 5 days) and 6 days (IQR: 3 to 11 days). Mortality was 7% in the CICU and 12% in the hospital. Of the 920 patients who survived to hospital discharge, 171 (19%) were readmitted within 30 days. Sepsis, acute kidney injury, and acute respiratory failure were associated with mortality. Acute kidney injury, acute respiratory failure, and new-onset subclinical atrial fibrillation, which occurred in 8% of admissions, were all associated with CICU LOS. CONCLUSIONS Many patients in the modern CICU have acute noncardiovascular illnesses that are associated with mortality and increased LOS. (C) 2017 by the American College of Cardiology Foundation.