Use of large-gauge, hollow-bore, arteriovenous fistula needles (AVFNs) and high-pressure accesses are unique factors inherent to the hemodialysis (HD) setting. The dialysis patient population has a higher incidence of hepatitis C (HCV) than the general population (8.4% compared to 1.8%) and the incidence of Human Immunodeficiency Virus (HIV) has increased tenfold from 1985 to 2000. HD health care workers (HCWs) are twice as likely to sustain a high-risk needlestick injury (NSI) as HCWs in all other settings. All of these factors leave HD HCWs at a high risk of exposure to bloodborne pathogens (BBPs). Although published data on NSI reduction with guarded AVFNs is lacking, many HD facilities have rushed to implement guarded AVFNs to comply with Occupational Safety and Health Administration's (OSHA) newly revised Bloodborne Pathogens Standard (29 CFR 1910.1030). For this study, we evaluated the effectiveness of one design of AVFN guard (MasterGuard Anti-Stick Needle Protector, Medisystems Corporation) by comparing its NSI rate to that of unguarded AVFNs. The unguarded AVFN injury rate was 8.58 NSIs per 100,000 unguarded AVFNs (in 81,534 cannulations) compared to zero NSIs per 100,000 guarded AVFNs (in 54,044 cannulations). The guarded AVFN showed a statistically significant NSI reduction compared to the unguarded AVFN (p < 0.029). This study demonstrates that using a guarded AVFN will help reduce HCWs' risk of exposure to BBPs in the dialysis setting.