This report updates the 2009 recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) regarding use of anthrax vaccine in the United States (Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP)], 2009. MMWR Recomm Rep 2010;59[No. RR-6]). The report 1) summarizes data on estimated efficacy in humans using a correlates of protection model and safety data published since the last ACIP review, 2) provides updated guidance for use of anthrax vaccine adsorbed (AVA) for preexposure prophylaxis (PrEP) and in conjunction with antimicrobials for postexposure prophylaxis (PEP), 3) provides updated guidance regarding PrEP vaccination of emergency and other responders, 4) summarizes the available data on an investigational anthrax vaccine (AV7909), and 5) discusses the use of anthrax antitoxins for PEP. Changes from previous guidance in this report include the following: 1) a booster dose of AVA for PrEP can be given every 3 years instead of annually to persons not at high risk for exposure to Bacillus anthracis who have previously received the initial AVA 3-dose priming and 2-dose booster series and want to maintain protection; 2) during a large-scale emergency response, AVA for PEP can be administered using an intramuscular route if the subcutaneous route of administration poses significant materiel, personnel, or clinical challenges that might delay or preclude vaccination; 3) recommendations on dose-sparing AVA PEP regimens if the anthrax vaccine supply is insufficient to vaccinate all potentially exposed persons; and 4) clarification on the duration of antimicrobial therapy when used in conjunction with vaccine for PEP. These updated recommendations can be used by health care providers and guide emergency preparedness officials and planners who are developing plans to provide anthrax vaccine, including preparations for a wide-area aerosol release of B. anthracis spores. The recommendations also provide guidance on dose-sparing options, if needed, to extend the supply of vaccine to increase the number of persons receiving PEP in a mass casualty event.