OBJECTIVE The use of a clinical decision support (CDS) tool to determine patients' eligibility for oral medication therapy and the opportunity cost of i.v.-to-oral conversion practices in a large health system was evaluated. METHODS This multicenter, retrospective, process improvement study comprised CDS data generated by 149 hospitals from May 1 through October 31, 2015. Data related to i.v.-to-oral conversions were identified and compiled for evaluation. For each patient with an opportunity for i.v.-to-oral therapy conversion, corresponding barcode-assisted medication administration data were evaluated to determine the number of doses that were administered within prespecified time periods. RESULTS A total of 121,685 i.v.-to-oral conversion opportunities, corresponding to 71,342 unique patients and encompassing 31 different medications, were evaluated. The top 13 medications representing 94% of the total number of alerts and over 1.4 million doses were included for analysis. Current i.v.-to-oral conversion practices saved the hospitals 9% on medication costs. Upon further evaluation, additional cost savings of 29-78% for those 13 medications could be achieved with more timely conversion from i.v. to oral therapy. CONCLUSIONS Hospital pharmacists' i.v.-to-oral conversion practices with the CDS tool resulted in medication cost savings of 9%, or $1.48 million, for 13 medications evaluated over a 6-month period.