Cardiac troponin I (cTnI) is a specific marker of myocardial damage used in the diagnosis of acute coronary syndrome (ACS). Recent studies have shown that cTnI levels can also be elevated in patients without ACS, such as in sepsis and trauma patients, and that this is associated with an adverse prognosis. We have evaluated the clinical implications and prognostic significance of serum cTnI levels in noncardiac critically ill patients in a prospective observational study in a general medical intensive care unit at a tertiary-level hospital. A total of 108 consecutive patients without ACS or other cardiac disease was enrolled. Serum cTnI levels were measured on admission using enzyme-linked immunoabsorbant assay kits. Clinical laboratory parameters and outcome were compared between patients with elevated and normal cTnI levels. The prognostic significance of cTnI levels and the Acute Physiology And Chronic Health Evaluation (APACHE) II score was also analyzed. Forty-nine patients (45%) had elevated cTnI levels and 59 (55%) had normal levels. Compared with patients with normal cTnI levels, patients with elevated levels had a higher incidence of new failure of two or more organs, had a lower left ventricular ejection fraction during admission, were more likely to be associated with bacteremia, and had a higher intensive care unit mortality; they also had a significantly shorter survival over a 180-day follow up, before and after stratification by the APACHE II score. Multiple organ failure was the leading cause of mortality in patients with elevated cTnI levels. By multivariate analysis, elevated cTnI levels, a high APACHE II score, and underlying cancer were the three most important independent predictors for a shorter survival. Combination analysis showed a shorter survival in patients with a high APACHE II score plus elevated cTnI levels than in patients with a high APACHE II score or elevated cTnI levels alone. In conclusion, elevated serum cTnI levels is a risk factor for multiple organ failure and mortality in noncardiac critically ill patients, and the cTnI levels and APACHE II score have an additive effect in outcome prediction.