Objective: The objective was to assess the ability of potential clinical predictors and inflammatory markers within 24 h of intensive care unit (ICU) discharge to predict subsequent in-hospital mortality. Design and setting: A prospective cohort study of 603 consecutive patients who survived their first ICU admission, between 1 June and 31 December 2005, in a 22-bed multidisciplinary ICU of a university hospital. Measurements and results: A total of 26 in-hospital deaths after ICU discharge (4.3%) were identified. C-reactive protein (CRP) concentrations at ICU discharge were associated with subsequent in-hospital mortality in the univariate analysis (mean CRP concentrations of non-survivors=174 vs. survivors=85.6 mg/l, p=0.001). CRP concentrations remained significantly associated with post-ICU mortality (a 10-mg/l increment in CRP concentrations increased the odds ratio [OR] of death: 1.09, 95% confidence interval [CI]: 1.03-1.16); after adjusting for age, the Acute Physiology and Chronic Health Evaluation (APACHE) II predicted mortality, and the Delta Sequential Organ Failure Assessment (Delta SOFA) score. The area under the receiver operating characteristic curve of this multivariate model to discriminate between survivors and non-survivors after ICU discharge was 0.85 (95% CI: 0.73-0.96). The destination and timing of ICU discharge, and the Discharge SOFA score, white cell counts and fibrinogen concentrations at ICU discharge were not significantly associated with in-hospital mortality after ICU discharge. Conclusions: A high CRP concentration at ICU discharge was an independent predictor of in-hospital mortality after ICU discharge in our ICU.