Intravenous antimicrobial therapy often continues after a patient is discharged from the hospital or it begins in the outpatient setting. Reimbursement for this therapy varies by payer. The United States Outpatient Parenteral Antibiotic Therapy (OPAT) Outcomes Registry is a valuable resource for quantifying cost by payer, as well as for describing practice patterns and adverse events related to intravenous antimicrobial therapy. To describe the reimbursement structure and cost of intravenous vancomycin home care therapy for four different types of payers, a survey of home infusion companies was done. Also surveyed were infusion programs participating in the OPAT Outcomes Registry, representing four different types of payers, to determine the cost of outpatient intravenous therapy. A retrospective cohort study of these infusion programs was conducted to describe practice patterns and to identify adverse events that resulted from intravenous vancomycin. We found that the cost of outpatient therapy was substantial, although nonuniform, across payer types. Alternative outpatient therapies associated with lower risks for adverse events and lower costs should be considered.