Side Effects of Smallpox Vaccination

This information is about preventing or responding to smallpox. For the latest information about the current mpox outbreak, including information on symptoms, prevention, and vaccines, please visit CDC’s Mpox site.

For most people, the smallpox vaccination is safe and effective. Most people experience normal, typically mild reactions to the vaccine, which indicates that the vaccine is beginning to work. Some people may experience reactions requiring medical attention.

Normal, Typically Mild Reactions

You may experience these reactions, which usually go away without treatment:

  • Your arm where you received the vaccination may be sore and red.
  • The glands (lymph nodes) in your armpits may become large and sore.
  • You may run a slight fever.
  • You might feel bad enough to miss work, school, or recreational activity or have trouble sleeping. This happens to about 1 out of every 3 people who get the vaccine.

Serious Reactions

In the past, for every 1,000 people vaccinated, 1 person experienced a serious but not life-threatening reactions. These reactions may require medical attention:

  • Spreading the vaccinia virus by touching the vaccination site and then touching another part of the body or another person. It usually occurs on the genitals or face, including the eyes, where it can damage sight. You can prevent this by washing your hands with soap and water after touching the vaccine site and by following the instructions for caring for the vaccine site.
  • A toxic or allergic rash that can take various forms.

Life-Threatening Reactions

Rarely, people have had very bad reactions to the vaccine. In the past, between 14 and 52 people out of every 1 million people vaccinated for the first time experienced potentially life-threatening reactions. These reactions require immediate medical attention:

  • Serious rash caused by widespread infection of the skin (known as eczema vaccinatum). This happened in people with pre-existing skin conditions such as eczema or atopic dermatitis. Many people who got this complication were not vaccinated, but got infected with the virus from the vaccine site of their family member or friend who received vaccination. To help reduce the risk for your loved ones, be sure to follow the instructions for caring for the vaccine site.
  • Buildup of inflamed tissue around the vaccination site that may at first look like a bullseye and will grow into a large, non-healing sore (known as progressive vaccinia). This usually happened to people with a deficient immune system.
  • Inflammation of the brain (known as postvaccinal encephalitis).

People with certain medical conditions—including people with weakened immune systems or certain skin conditions—are more likely to have these reactions and should not get the smallpox vaccine unless they have been exposed to smallpox. You can read more about people who should not get the smallpox vaccine in Smallpox Vaccine Safety.

Based on past experience, it is estimated that 1 to 2 people out of every 1 million people vaccinated could die as a result of life-threatening reactions to the vaccine.

Other Serious Side Effects

A few people who have gotten the smallpox vaccine have developed heart inflammation (myocarditis), inflammation of the lining of the heart (pericarditis), or a combination of both (myopericarditis).

Other people have experienced heart pain (angina) and heart attack after getting the smallpox vaccination. However, it is not known if the smallpox vaccination caused these problems or if they occurred by chance alone.

If you have chest pain, shortness of breath, or other symptoms of heart disease after getting the smallpox vaccination, you should seek medical attention.

A Note on Numbers: Most of the statistical information about smallpox vaccine side effects cited on this webpage is based on data from two studies conducted in 1968.

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