Acute and chronic critical conditions are associated with reduced serum levels of free triiodothyronine (FT(3)), free thyroxine FT(4), and thyrotropin, known as nonthyroidal illness syndrome (NTIS). It is still controversial whether these changes reflect a protective mechanism or a maladaptive process during prolonged illness. However, larger studies to determine the prevalence of the NTIS and its association with outcome in medical intensive care units (ICUs) are missing. Complete thyroid hormone levels from 247 of 743 patients admitted to our ICU between October 2002 and February 2004 were retrospectively evaluated. From these patients, Acute Physiology and Chronic Health II scores, ICU mortality, length of stay, mechanical ventilation, and concomitant medication were recorded. Ninety-seven patients (44.1%) had low FT(3) levels indicating an NTIS, either with normal (23.6%) or reduced (20.5%) serum thyrotropin levels. Of 97 patients with NTIS, 24 (23.3%) also showed reduced serum FT(4) levels. The NTIS was significantly associated with Acute Physiology and Chronic Health II scores, mortality, length of stay, and mechanical ventilation. In a multivariate Cox regression analysis, the combination of low FT(3) and low FT(4) was an independent risk factor for survival. Nonthyroidal illness syndrome is frequent at a medical ICU. A reduction of FT(4) together with FT(3) is associated with an increase in mortality and might reflect a maladaptive process, thereby worsening the disease.