Smallpox Vaccine

Safety Information

Smallpox Disease and How to Protect Against It

Smallpox is a contagious, disfiguring, and often deadly disease that is caused by the variola virus. Naturally occurring smallpox was eradicated worldwide by 1980 through a global immunization campaign. Smallpox vaccine is not currently recommended for the general public, although the vaccine is given to selected service members and laboratory workers. In the event of a smallpox emergency, the government has enough smallpox vaccine to vaccinate everyone in the United States.

Smallpox Vaccine Side Effects

The smallpox vaccine is safe, and it is effective at preventing smallpox disease. Vaccines, like any medicine, can have side effects.

Common Side Effects of Smallpox Vaccine
  • Itching
  • Swollen lymph nodes
  • Sore arm from the shot
  • Fever
  • Headache
  • Body ache
  • Mild rash
  • Fatigue (tiredness)
  • Problems with the vaccination site blister, such as infection

After getting the vaccine, a person will have a dime-sized lesion that gradually forms a scab and leaves a scar. The material from the lesion (fluid and crusts) is contagious until a scab forms at the vaccination site. Therefore, people who get the smallpox vaccine should be sure to properly care for and cover the vaccination site to prevent spreading the vaccine virus to other parts of their body or to other people.

Serious Side Effects of Smallpox Vaccine
  • Heart problems
  • Swelling of the brain or spinal cord
  • Severe skin diseases
  • Spreading the virus to other parts of the body or to another person
  • Severe allergic reaction after vaccination
  • Accidental infection of the eye (which may cause swelling of the cornea causing watery painful eyes and blurred vision, scarring of the cornea, and blindness)

The risks for serious smallpox vaccine side effects are greater for:

  • People with any three of the following risk factors for heart disease: high blood pressure, high cholesterol, diabetes, high blood sugar, a family history of heart problems, or smoking
  • People with heart or blood vessel problems, including angina, previous heart attack, artery disease, congestive heart failure, stroke, or other cardiac problems
  • People with skin problems, such as eczema, atopic dermatitis, burns, impetigo, contact dermatitis, chickenpox, shingles, psoriasis, or uncontrolled acne
  • People with weakened immune systems, such as those who have received a transplant, are HIV positive, are receiving treatment for cancer, or are taking medications that suppress the immune system
  • Infants less than 1 year of age
  • Women who are pregnant or breastfeeding
  • People who are taking steroid eye drops or ointment
  • People who have had problems after previous doses of smallpox vaccine or are allergic to any part of smallpox vaccine, such as antibiotics neomycin or polymixin B

Available Smallpox Vaccine

Currently, there is one approved vaccine to protect people against smallpox:

  • ACAM2000 [PDF – 11 pages]: The Food and Drug Administration approved this vaccine in 2007. The approval for the previously recommended smallpox vaccine (Dryvax) was withdrawn in 2008.

For more information about smallpox vaccine safety, visit:

How CDC Monitors Vaccine Safety

CDC and FDA monitor the safety of vaccines after they are approved or authorized. If a problem is found with a vaccine, CDC and FDA will inform health officials, health care providers, and the public.

CDC uses 3 systems to monitor vaccine safety:

Related Scientific Articles

CDC. Newly Licensed Smallpox Vaccine to Replace Old Smallpox VaccineMMWR 2008; 57(08):207–8.

Greenberg RN, Kennedy JS. ACAM2000: a newly licensed cell culture-based live vaccinia smallpox vaccineExpert Opin Investig Drugs. 2008 Apr;17(4):555-64.

Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968New Engl J Med. 1969 Nov 27;281(22):1201-8.

Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results of ten statewide surveysJ Infect Dis. 1970 Oct;122(4):303-9

McNeil MM, Cano M, Miller E, Petersen BW, Engler RJ, Bryant-Genevier MG. Ischemic cardiac events and other adverse events following ACAM2000(®) smallpox vaccine in the Vaccine Adverse Event Reporting SystemVaccine. 2014 Aug 20;32(37):4758-65.

Petersen BW, Damon IK, Pertowski CA, Meaney-Delman D, Guarnizo JT, et al. Clinical Guidance for Smallpox Vaccine Use in a Postevent Vaccination ProgramMMWR. 2015;64(RR02):1-26.

Poland GA, Grabenstein JD, Neff JM. The US smallpox vaccination program: a review of a large modern era smallpox vaccination implementation programVaccine. 2005 Mar 18;23(17-18):2078-81.

Rotz LD, Dotson DA, Damon IK, Becher JA, Advisory Committee on Immunization Practices. Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001MMWR RR. 2001 Jun 22;50(RR-10):1-25.

Tack DM, Karem KL, Montgomery JR, Collins L, Bryant-Genevier MG, et al.  Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000(®) compared with Dryvax(®)Hum Vaccin Immunother. 2013 Jul;9(7):1489-96.

Verardi PH, Titong A, Hagen CJ. A vaccinia virus renaissance: new vaccine and immunotherapeutic uses after smallpox eradicationHum Vaccin Immunother. 2012 Jul;8(7):961-70.