OBJECTIVES: Polyethylene glycol-conjugated (PEGylated) therapies are commonly used to treat patients with anemia, neutropenia, and viral hepatitis. While no PEGylated drugs are currently approved for the treatment of multiple sclerosis (MS), a PEGylated formulation of interferon beta-1a is being developed for relapsing-remitting MS treatment. The goal of this study was to identify the economic benefits of PEGylated drugs currently available in other disease areas. METHODS: A comprehensive search of the medical literature was conducted using PubMed/MEDLINE, article links, and supplemental searches. Inclusion criteria included English language, publication date between 1985 and 2010, prospective or retrospective study design, and cost or cost-effectiveness studies comparing PEGylated drugs with their non-PEGylated counterparts in the same therapeutic area. All costs were adjusted to 2010 US dollars for reporting. RESULTS: Thirty-seven published articles reporting data from 11 countries in 12 therapeutic areas were reviewed, including studies on pegfilgrastim, liposomal PEGylated doxyrubicin, peginterferon alfa 2a and 2b, pegaspargase, and PEGylated epoetin. Twelve studies showed some cost offsets for 6 PEGylated drugs, with 4 of the drugs reducing administration costs. Other offset costs included those for adverse event treatment, disease complications, and inpatient/outpatient treatment. Nineteen of the 35 studies considering total treatment costs showed total cost savings with 3 of 5 PEGylated drugs, ranging up to $7743 per patients annually. With 4 PEGylated drugs, 17 of 18 studies reported incremental cost-effectiveness ratios below $50,000 per quality-adjusted life-year. CONCLUSIONS: PEGylated drugs are reported to reduce patient health resource use and costs, including costs associated with drug administration and adverse events. Since multiple studies have demonstrated that PEGylated drugs are more cost-effective than their non-PEGylated counterparts, PEGylated interferon beta-1a may offer similar economic benefits to payers and health care systems.