For a study, researchers sought to create the REALIST score as part of the REALISM project as a helpful tool to assist doctors in better identifying and stratifying patients at high risk for subsequent infection using a straightforward set of technically sound and widely accessible biomarkers. In a single-center prospective cohort study, the immunological profiles of critically ill patients who had undergone major surgery, severe trauma, or sepsis/septic shock were assessed. About 5 immunological indicators were proactively chosen for the REALIST score based on their clinical usefulness and technical viability. The ability of various parameters and parameter combinations to predict results was examined. The 30-day frequency of subsequent infection was the key finding of interest. A total of 3 factors, mHLA-DR, the percentage of immature (CD10CD16) neutrophils, and serum IL-10 level, remained in the REALIST score after statistically redundant, and weakly predictive indicators were eliminated. In the study group (n=189), the incidence of secondary infection increased from 8% for patients with a REALIST score of 0 to 46% for patients with a score of 3 aberrant parameters at day 30 when measured as of D5-7. Higher REALIST scores were independently associated with a higher risk of secondary infection (42 events, 22.2%, adjusted HR 3.22 (1.09-9.50), P=0.034) and mortality (10 events, 5.3%) when clinical risk factors for secondary infection (SOFA score and invasive mechanical ventilation at D5-7) were taken into account. Investigators developed and introduced the REALIST score, a straightforward and practical stratification technique that gave clinicians a precise evaluation of the immunological state of their patients. This new tool could help plan future research, such as immune stimulation techniques, and enhance the treatment given to these patients.