To determine the relation between the proposed ACCP/SCCM Consensus Conference classification of sepsis and hospital outcomes, we conducted a single-center, prospective observational study at Barnes Hospital, St. Louis, MO, an academic tertiary care hospital. A total of 324 consecutive patients admitted to the medical intensive care unit (ICU) were studied for prospective patient surveillance and data collection. The main outcome measures were the number of acquired organ system derangements and hospital mortality. Fifty-seven (17.6%) patients died during the study period. The proposed classifications of sepsis (e.g., systemic inflammatory response syndrome [SIRS], sepsis, severe sepsis, septic shock) correlated with hospital mortality (r = 0.330; p<0.001) and development of an Organ System Failure Index (OSFI) of 3 or greater (r = 0.426; p<0.001). Independent determinants of hospital mortality for this patient cohort (p<0.05) were development of an OSFI of 3 greater (adjusted odds ratio [AOR], 13.9; 95% confidence interval [CI], 6.4-30.2; p<0.001); presence of server sepsis or septic shock (AOR, 2.6; 95% CI, 1.2-5.6; p=0.002), and an APACHE II score ≤ of 18 or greater (AOR, 2.4; 95% CI, 1.0-5.8; p=0.045). Intra-abdominal infection (AOR, 19.1; 95% CI, 1.6-230.1; p=0.011), an APACHE II score ≤ of 18 or greater (AOR, 8.9; 95% CI, 4.2-18.6; p<0.001), and presence of severe sepsis or septic shock (AOR, 2.9; 95% CI, 1.5-5.4; p=0.001) were independently associated with development of an OSFI of 3 or greater. These data confirm that acquired multiorgan dysfunction is the most important predictor of mortality among medical ICU patients. In addition, they identify the proposed ACCP/SCCM Consensus Conference classification of sepsis as an additional independent determinant of both hospital mortality and multiorgan dysfunction.