OBJECTIVES To quantify the budget impact of using HDIVPPI before EGD in ambulatory patients presenting with acute, overt UGIB in different clinical scenarios. METHODS A decision tree compared pre-EGD HDIVPPI to none in a model that emulates contemporary standards of care. Patients were stratified by clinical likelihood of rebleeding (high/low), time to EGD, method of endoscopic hemostasis (epinephrine injection/other), and early discharge when clean-base ulcers are noted (frequent/rare). Probabilities and lengths of stay originated from the literature and bleeding registries. Hospital and additional pharmacological costs came from the Nationwide Inpatient Sample and Red Book (2008 $US). Expert consensus was sought when needed. Esomeprazole was the PPI in the base-case. One-way deterministic sensitivity analyses were performed on all variables across wide pre-set ranges. Model time horizon was 30 days, adopting a third-party payer perspective. RESULTS In the base-case, average costs were $9139 for the pre-EGD HDIVPPI strategy and $9029 for the arm without. This increment rose slightly amongst patients with a high clinical likelihood of rebleeding ($117/pt) or when using only hemostatic methods other than epinephrine injection ($128/pt). It dropped amongst patients undergoing epinephrine injection ($95/pt) or a late EGD ($37/pt). All mean costs were lowest, and this time favoring the HDIVPPI approach, when clean-base ulcer patients were discharged early ($8,263 for HDIVPPI versus $8,282 for none).In sensitivity analyses, variables with the greatest impact were the per diem cost of hospital stay complicated by rebleeding, and elapsed times to early or late EGD; overall per patient incremental costs varied from $16-$174. CONCLUSIONS The introduction of HDIVPPI prior to EGD in a US managed care setting amongst acute UGIB patients in most scenarios raise modestly mean patient costs. This approach, however, becomes cheaper than no PPI administration pre-EGD when selected patients bleeding from clean-base ulcers are discharged home from the emergency room.