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Chronic diabetes mellitus (DM) is a known cause of multisystem injury. The effect of DM in acute critical illness may also be detrimental, but is not specifically known. We hypothesized that the preexisting diagnosis of DM is an independent risk factor for mortality in critically ill patients.Parallel retrospective and prospective cohort study.Two large patient datasets were used: the retrospective University HealthSystem Consortium database (UHC) and the prospective Mayo Clinic Acute Physiology And Chronic Health Evaluation III critical care database (Mayo).Inclusion criteria were admission to an intensive care unit and age ≥18 yrs. Patients with diabetic ketoacidosis or hyperosmolar nonketotic coma were excluded. A total of 1,509,890 patients (including 143,078 deaths) in the UHC cohort and 36,414 patients (including 3562 deaths) in the Mayo cohort were included in the study analysis.The primary outcome was in-hospital mortality compared between patients with a history of DM and all other patients. Other outcomes included in-hospital mortality in prespecified subgroups. In the UHC dataset, patients with DM had a lower unadjusted odds ratio (0.90, 95% confidence interval 0.89–0.91, p < .001) and a lower adjusted effect on mortality (odds ratio 0.75, 0.74–0.76, p < .001) compared with that seen in patients without DM. In the Mayo dataset, patients with DM had a comparable unadjusted odds ratio (1.07, 0.97–1.17, p = NS) and a lower adjusted effect on mortality (odds ratio 0.88, 0.79–0.98, p = .022) compared with that seen in patients without DM. A lower mortality in diabetic patients held across multiple demographic subgroups, including patients who underwent coronary-artery bypass grafting (UHC data: unadjusted odds ratio 0.66, 0.62–0.71, p < .001).Critically ill adults with DM do not have an increased mortality compared with that seen in patients without DM, and may have a decreased mortality. Further investigation needs to be done to determine the mechanism for this effect.