ABSTRACT: INTRODUCTION: To establish a prognostic model for predicting 14-day mortality in ICU patients with severe sepsis overall and according to place of infection acquisition and to sepsis episode number. METHODS: In this prospective multicentre observational study on a multicentre database (OUTCOMEREA) including data from 12 ICUs, 2268 patients with 2737 episodes of severe sepsis were randomly divided into a training cohort (n=1458) and a validation cohort (n=810). Up to four consecutive severe sepsis episodes per patient occurring within the first 28 ICU days were included. We developed a prognostic model for predicting death within 14 days after each episode, based on patient data available at sepsis onset. RESULTS: Independent predictors of death were logistic organ dysfunction (OR, 1.22 per point, p<10-4), septic shock (OR, 1.40; p=0.01), rank of severe sepsis episode (1 reference, 2: OR, 1.26; p=0.10 [greater than or equal to]3: OR, 2.64 ;10-3), multiple sources of infection (OR; 1.45, p=0.03), simplified acute physiology score II (OR, 1.02 per point; p<10-4), McCabe score ([greater than or equal to]2)(OR, 1.96; p<10-4), and number of chronic co-morbidities (1: OR, 1.75; p=10-3, [greater than or equal to]2: OR, 2.24, p= 10-3). Validity of the model was good in whole cohorts (AUC-ROC, 0.76; 95%CI [0.74; 0.79] and HL Chi-square: 15.3 (p=0.06) for all episodes pooled). CONCLUSIONS: In ICU patients, a prognostic model based on a few easily obtained variables is effective in predicting death within 14 days after the first to fourth episode of severe sepsis complicating community-, hospital-, or ICU-acquired infection.