Background: Parenteral nutrition (PN) is an essential feeding route for specific patient populations. Despite its utility, PN is invasive, costly, and associated with clinical complications. In most U.S. hospitals, PN is overprescribed. This study measured rates of inappropriate PN use in hospitalized adults, as determined by the 2002 American Society for Parenteral and Enteral Nutrition guidelines, at 4 tertiary care South Carolina hospitals (facilities A–D). Secondary aims were to identify indicators of inappropriate use and estimated preventable costs. Methods: Over a 3‐month period, trained registered dietitians at each site collected data retrospectively and prospectively to determine PN appropriateness and indicators of use in 278 randomly selected PN cases. Results: PN therapy was inappropriately prescribed in 32% of cases, resulting in approximately 552 days and $138,000 in preventable hospital costs. Thirteen percent of patients who were prescribed inappropriate PN were discharged on home PN. Mean duration of PN therapy was higher in inappropriate cases vs appropriate cases (6 ± 7 days [range, 1–78 days] vs 10 ± 10.6 days [range, 1–51 days]; P < .004). Facility B had lower rates of inappropriately prescribed PN (23%) compared with facilities A (33%), C (35%), and D (38%). Dietitians recommended against PN in >70% of all inappropriate cases at facilities A and D compared with <45% at facilities B and D (P < .001). Facility B employed more certified nutrition support dietitians (68% of staff) and was among the 2 hospitals using a nutrition support team (NST). Conclusion: This study was novel by comparing PN practices in statewide hospitals. Results indicate that NSTs and certified nutrition support clinicians can curtail preventable spending from inappropriate PN use. Future studies should identify barriers in implementing evidence‐based practice.