BackgroundOnly a subset of patients at risk for acute respiratory distress syndrome (ARDS) go on to develop it, and the contribution of preexisting comorbidities, such as diabetes, to ARDS risk is not well understood. Prior studies of the association between diabetes and ARDS yielded conflicting results. Research QuestionDoes assessing ARDS risk based on hemoglobin A1c (HbA1c) as a marker of long-term blood glucose levels, rather than a charted diagnosis of diabetes, clarify the relationship between diabetes and ARDS? Study Design and MethodsUsing data from two prospective observational cohorts of critically ill adults (VALID and EARLI), we analyzed the association between clinical HbA1c category and development of ARDS in patients with a risk factor for ARDS and at least one clinical HbA1c measurement within the 180 days prior through 14 days after enrollment. Results599 patients in VALID and 276 in EARLI met inclusion criteria, of whom 164 and 58 developed ARDS, respectively. Patients with a charted diagnosis of diabetes were not more likely to develop ARDS (VALID: 24.6% ARDS in non-diabetics vs. 30.0% in diabetics, p=0.14; EARLI: 19.6% vs. 22.8%, p=0.55). However, in VALID, patients categorized as diabetic with inadequate glycemic control based on their HbA1c had an increased risk of developing ARDS compared to those with a non-diabetic HbA1c (20.9% vs. 34.0%; p=0.0073), a finding that persisted in multivariable analysis (OR for diabetic with inadequate glycemic control vs. non-diabetic range HbA1c = 1.25, 95% CI 1.01-1.57). These findings were not reproduced in the smaller EARLI cohort, but were appreciated when the cohorts were combined for analysis. InterpretationElevated HbA1c may be associated with risk of developing ARDS, independent of clinical diagnosis of diabetes, but prospective validation is needed. If confirmed, these findings suggest that inadequate glycemic control could be an unrecognized risk factor for ARDS.