OBJECTIVES: Clinical trials in soft tissue surgery with Depofoam® bupivacaine (DB) have shown that a single injection into the surgical site provides postsurgical pain control for up to 72 hours while reducing the need for opioids. This study extrapolates via a simplified decision tree the economic impact of DB vs. bupivacaine HCl (BH) in patients undergoing colectomy and cholecystectomy. METHODS: This simple model combined data from a claims database analysis with literature. The incidence of opioid use (92%) and risk of ICD-9 diagnosis-coded opioid-related adverse events (ORAEs) (16.32%) for the BH group were estimated via retrospective analysis of the Premier hospital database. The incidence rates of opioid use (68%) and ORAEs (1.86%) in the DB group were based on the relative reduction between DB and BH observed in a hemorrhoidectomy trial. The excess cost per patient with ORAE ($4,707) was estimated from Premier. DB and BH drug acquisition costs, opioid costs (including inpatient pharmacy, administration, errors and outpatient pharmacy) were literature based. Analyses were conducted in 378 subgroups defined by surgery types (colectomy and cholecystectomy) and demographics. RESULTS: Compared to BH, the use of DB is projected to result in an increase in analgesia drug acquisition cost of $249/patient. This was offset by expected reductions in opioids (-$95/patient) and ORAE (-$680/patient) costs, resulting in net cost savings of $526/patient overall. DB resulted in modeled costs savings in all but one of the 378 subgroups. These ranged from cost savings of $1,633/patient in the “open cholecystectomy/admission source trauma” subgroup to a cost increase of $28/patient in the “cholecystectomy/age 18-30” subgroup. CONCLUSIONS: As a result of better pain management and reduced opioids usage, the use of DB (v. BH) at the time of colectomy/cholecystectomy is modeled to be cost saving overall and in 99.7% of subgroups considered.