OBJECTIVES: To protect healthcare workers from risk of needlestick injury, preventive safety measures are increasingly mandated in the healthcare environment, which may include the use of safety-engineered medical sharp devices (SEDs) specifically designed to prevent sharps injuries. We undertook a systematic review of the literature to understand the economic impact of replacing conventional sharps devices with SEDs.  METHODS: We conducted searches of electronic databases including Embase/MEDLINE, PubMed, CINAHL Plus, HEED, NHS EED, the Cochrane Library, ProQuest Nursing and Allied Health Source, and the Tufts CEA Registry. Databases of the WHO and HTA agencies, reference lists of identified studies, conference abstract books and the internet were also searched. The time horizon covered January 1990 to March 2013. Two reviewers independently screened titles and abstracts, applied inclusion criteria to full text papers and extracted data from identified studies according to an a priori defined data set. Differences were resolved by consensus. Study quality was assessed using a published 10-point checklist.  RESULTS: From 19621 records, 21 studies met the review criteria and were selected. Most studies (16) were budget impact analyses (BIAs). Reductions in sharps injuries with SEDs ranging from 12% to 100% were reported. Just 4 studies were assessed as providing the best quality evidence: a cost benefit analysis and 3 BIAs. Key assessment criteria that the other studies did not meet were consideration of all relevant costs and execution of a sensitivity analysis. Of the best quality studies, 3 reported net economic benefits from implementing SEDs, at least in the base case analysis.  CONCLUSIONS: Investment in SEDs generates economic benefits from savings in managing medical sharps injuries and their sequelae. Future economic evaluations need to carefully assess all important and pertinent costs to enable well-informed decision-making about the implementation of SEDs in the healthcare workplace.