IMPORTANCE The Sepsis-3 Criteria emphasized the value of a change of 2 or more points in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score, introduced quick SOFA (qSOFA), and removed the systemic inflammatory response syndrome (SIRS) criteria from the sepsis definition. OBJECTIVE Externally validate and assess the discriminatory capacities of an increase in SOFA score by 2 or more points, 2 or more SIRS criteria, or a qSOFA score of 2 or more points for outcomes among patients who are critically ill with suspected infection. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort analysis of 184 875 patients with an infection-related primary admission diagnosis in 182 Australian and New Zealand intensive care units (ICUs) from 2000 through 2015. EXPOSURES SOFA, qSOFA, and SIRS criteria applied to data collected within 24 hours of ICU admission. MAIN OUTCOMES AND MEASURES The primary outcomewas in-hospital mortality. In-hospital mortality or ICU length of stay (LOS) of 3 days or more was a composite secondary outcome. Discrimination was assessed using the area under the receiver operating characteristic curve (AUROC). Adjusted analyses were performed using a model of baseline risk determined using variables independent of the scoring systems. RESULTS Among 184 875 patients (mean age, 62.9 years [SD, 17.4]; women, 82 540 [44.6%]; most common diagnosis bacterial pneumonia, 32 634 [17.7%]), a total of 34 578 patients (18.7%) died in the hospital, and 102 976 patients (55.7%) died or experienced an ICU LOS of 3 days or more. SOFA score increased by 2 or more points in 90.1%; 86.7%manifested 2 or more SIRS criteria, and 54.4%had a qSOFA score of 2 or more points. SOFA demonstrated significantly greater discrimination for in-hospital mortality than SIRS criteria or qSOFA. SOFA also outperformed the other scores for the secondary end point. Findings were consistent for both outcomes in multiple sensitivity analyses. CONCLUSIONS AND RELEVANCE Among adults with suspected infection admitted to an ICU, an increase in SOFA score of 2 or more had greater prognostic accuracy for in-hospital mortality than SIRS criteria or the qSOFA score. These findings suggest that SIRS criteria and qSOFAmay have limited utility for predicting mortality in an ICU setting.