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Background: Diabetic ketoacidosis (DKA) is a serious acute complication of both type 1 and type 2 diabetes that requires prompt management. Limited data exist supporting the use of a 2-bag DKA protocol in adult patients across all levels of care. Objective: To evaluate the efficacy and safety of a 2-bag DKA protocol in comparison with a traditional DKA management strategy. Methods: Retrospective review of patients admitted with DKA between January 1, 2021, and February 28, 2022, at a single center. Patients were separated into 2 cohorts, traditional or 2-bag. The primary outcome was time to anion gap closure and/or beta-hydroxybutyrate normalization. Secondary outcomes include length of hospitalization, insulin infusion time, and hypoglycemic events. Results: One hundred forty-three patients had a DKA order set initiated during their admission, 59 in the traditional cohort and 84 in the 2-bag cohort. Mean time to anion gap closure was shorter in the 2-bag cohort (12.7 vs 16.9 hours; P = 0.005) and beta-hydroxybutyrate normalization (15.6 vs 25.6 hours; P = 0.026). No difference in hospital length of stay (4 vs 6 days; P = 0.113), duration of insulin infusion (41.6 vs 40.6 hours; P = 0.455), or rates of hypoglycemia (6 vs 4; P = 0.872) was seen. Conclusion and Relevance: Implementation of a 2-bag DKA protocol in the inpatient setting was associated with a shorter time to anion gap closure and beta-hydroxybutyrate normalization. These findings support the option of expansion of a 2-bag DKA protocol to adult patients across all levels of care irrespective of the admission diagnosis.