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Objectives: To measure the impact of full versus partial ABCDE bundle implementation on specific cost centers and related resource utilization. Design: Retrospective cohort study. Setting: Two medical ICUs within Montefiore Health System (Bronx, NY). Patients: Four hundred and seventy-two mechanically ventilated patients admitted to the medical ICUs during a hospitalization which began and ended between January 1, 2013 and December 31, 2013. Interventions: The full (A)wakening, (B)reathing, (C)oordination, (D)elirium Monitoring/Management and (E)arly Mobilization bundle was implemented in the intervention ICU while a portion of the bundle (A, B, and D components) was implemented in the comparison ICU. Measurements and Main Results: Relative to the comparison ICU, implementation of the entire bundle in the intervention ICU was associated with a 27.3% (95% CI: 9.9%, 41.3%; P = 0.004) decrease in total hospital laboratory costs and a 2,888.6% (95% CI: 77.9%, 50,113.2%; P = 0.018) increase in total hospital physical therapy costs. Cost of total hospital medications, diagnostic radiology and respiratory therapy were unchanged. Relative to the comparison ICU, total hospital resource use decreased in the intervention ICU (incidence rate ratio [95% CI], laboratory: 0.68 [0.54, 0.87], P = 0.002; diagnostic radiology: 0.75 [0.59, 0.96], P = 0.020). Conclusions: Full ABCDE bundle implementation resulted in a decrease in total hospital laboratory costs and total hospital laboratory and diagnostic resource utilization while leading to an increase in physical therapy costs.