OBJECTIVE: To identify variables associated with mortality in the ICU and 1 year following discharge. DESIGN: Prospective observational cohort study. SETTING: ICU of a tertiary care center and university hospital. PATIENTS: A total of 3,119 medical and neurological intensive care patients. MEASUREMENTS AND MAIN RESULTS: Pre-admission health status was quantified by the sum of risk factors and chronic diseases. Severity of the acute disease was estimated by counting the number of organ dysfunctions and the Acute Physiology Score. Concerning the primarily affected organ system, ICU mortality was highest in hematological diseases (63%) and 1-year mortality was 82%. Lowest death rates were observed with metabolic (ICU 4%, 1-yr 18%) and psychiatric diagnoses (ICU 5%, 1-yr 13%). Greater severity of illness with the need for mechanical life support was associated with decreased 1-year survival. In the respiratory and in renal diseases, the artificial support of the primarily affected organ system incurred an ICU mortality equaling the average (23%) or below (14%) that of the whole ICU population. Pre-admission health status increased the probability of developing multiple organ failure and worsened outcome 1 year after discharge in non-cardiovascular patients. Age showed a weak correlation with chronic diseases and severity of the acute illness and was related to long-term, but not short-term survival. CONCLUSIONS: The most important risk factors associated with short- and long-term mortality in non-surgical intensive care patients are disease severity and the primarily affected organ system that necessitates admission. The artificial support of this organ system can improve only short-term outcome.