Brucella abortus strain RB51 vaccine, is an attenuated live bacterial vaccine that was licensed conditionally by the Center for Veterinary Biologics, Veterinary Services, Animal and Plant Health Inspection Service, USDA, on 23 February 1996, for vaccination of cattle in the United States. Accidental human inoculations can occur during vaccination of cattle, and previous live Brucella vaccines designed for cattle have been known to cause brucellosis in humans. The Centers for Disease Control and Prevention (CDC) established passive surveillance for accidental inoculation with the RB51 vaccine in the United States to determine if this veterinary vaccine is associated with human disease, to describe the circumstances of accidental inoculation, to evaluate the potential efficacy of post-exposure chemoprophylaxis, and to develop recommendations for post-exposure management following exposure to RB51. Reports were received from 26 individuals. Accidental exposure to RB51 occurred by needle stick injury in 21 people (81%), conjunctival spray exposure in four (15%), and spray exposure of an open wound in one (4%) individual. At least one systemic symptom was reported in 19 (73%) people, including three (12%) who reported persistent local reactions with systemic involvement. One case required surgery, and B. abortus strain RB51 was isolated from the wound of that individual. Seven cases reported no adverse event associated with accidental exposure. Nine cases reported previous exposure to Brucella vaccines, including one case who also reported a previous diagnosis of brucellosis following exposure to S19 vaccine. Accidental needle stick injuries and conjunctival or open wound exposures of humans with the RB51 vaccine are associated with both local and systemic adverse events in the United States that are consistent with brucellosis; however, it remains undetermined if strain RB51 vaccine can cause systemic brucellosis in humans. Early culture attempts on those exposed and developing disease in the future and serologic diagnostic assays for anti-RB-51 antibodies are needed to define if these adverse events are due to RB51 and to define appropriate prophylaxis regimens.