Most vaccines in the United States are given as intramuscular (IM) injections, but a handful are administered subcutaneously, meaning the needle deposits the vaccine into the fatty tissue just beneath the skin rather than into the muscle. The list is short: MMR, varicella, MMRV, yellow fever, the dengue vaccine (DEN4CYD), and meningococcal polysaccharide (MPSV4) are subcutaneous-only. Two others, PPSV23 (the pneumococcal polysaccharide vaccine) and IPV (the polio vaccine), can be given either subcutaneously or intramuscularly. The smallpox/monkeypox vaccine Jynneos is primarily subcutaneous as well, though it can also be given intradermally.
Vaccines Given Subcutaneously Only
These vaccines are labeled for subcutaneous injection and are not routinely given intramuscularly:
- MMR (PRIORIX): Measles, mumps, and rubella. The PRIORIX brand is subcutaneous only. The older M-M-R II brand can actually be given either subcutaneously or intramuscularly, giving providers some flexibility.
- MMRV (ProQuad): Combines measles, mumps, rubella, and varicella in one shot for children. Like M-M-R II, ProQuad may be given subcutaneously or intramuscularly.
- Varicella (Varivax): The chickenpox vaccine, given as a 0.5 mL subcutaneous injection.
- Yellow fever: Required for travel to certain countries in Africa and South America. Administered subcutaneously.
- MPSV4: The meningococcal polysaccharide vaccine, given subcutaneously. (This is distinct from the more commonly used meningococcal conjugate vaccines, which are intramuscular.)
- DEN4CYD: The dengue vaccine, a 0.5 mL subcutaneous injection.
- Jynneos: The smallpox/monkeypox vaccine. Primarily subcutaneous, though intradermal administration is used in some circumstances.
Vaccines That Allow Either Route
Two commonly used vaccines give providers the choice of subcutaneous or intramuscular delivery:
- PPSV23 (Pneumovax 23): The pneumococcal polysaccharide vaccine, used mainly in adults 65 and older or people with certain chronic conditions. The FDA-approved labeling allows either IM or subcutaneous injection into the deltoid or lateral mid-thigh.
- IPV (IPOL): The inactivated polio vaccine, part of the routine childhood schedule. It can be given intramuscularly or subcutaneously.
When a vaccine allows both routes, providers often default to intramuscular because it tends to produce a stronger immune response and fewer local reactions. But the subcutaneous option exists and produces adequate protection.
Why Some Vaccines Need Subcutaneous Delivery
The pattern is not random. Most subcutaneous-only vaccines are live, attenuated vaccines, meaning they contain a weakened form of the virus. MMR, varicella, MMRV, and yellow fever all fall into this category. Live vaccines generally work well in the fatty tissue beneath the skin because the weakened virus can still replicate enough to trigger a strong immune response without needing the richer blood supply found in muscle.
Vaccines that contain aluminum-based adjuvants (additives that boost the immune response) are a different story. Hepatitis A, hepatitis B, and diphtheria-tetanus-pertussis vaccines all use aluminum adjuvants and must be given intramuscularly. When these adjuvant-containing vaccines are accidentally deposited in subcutaneous fat, the aluminum salt can cause more irritation, inflammation, and hard lumps at the injection site. Fat tissue has poor blood drainage compared to muscle, so the adjuvant sits in place longer and provokes a more intense local reaction.
That poor blood supply also explains why some non-live vaccines fail when given subcutaneously by mistake. Hepatitis B vaccine given subcutaneously produces significantly lower rates of protective antibody levels and the antibodies decline faster compared to intramuscular delivery. Fat tissue simply lacks the immune cells needed to efficiently pick up and process the antigen. The vaccine material can sit in fat for hours or even days, during which enzymes may break it down before it ever reaches the immune system.
Where Subcutaneous Vaccines Are Injected
Subcutaneous injections go into the fatty layer just under the skin, not into the muscle beneath it. For vaccines, the most common site is the fatty tissue over the upper outer arm (the triceps area). The anterior thigh is another option, particularly in infants and young children. Less commonly, the upper back, abdomen, or buttocks can be used for subcutaneous injections of medications, though for vaccines the arm and thigh are standard.
The needle is shorter and thinner than what you’d see for an intramuscular shot. For children, a 3/8-inch needle with a 25-gauge diameter is typical. For adolescents and adults, needles range from about half an inch to 5/8 of an inch, using 25- to 27-gauge needles. For larger patients, a 7/8-inch needle may be selected to ensure the vaccine reaches the subcutaneous layer rather than staying too superficial in the skin. The injection volume is small, typically 0.5 mL for all the subcutaneous vaccines on the current schedule.
Subcutaneous Vaccines for Blood Thinner Users
If you take blood thinners or have a bleeding disorder, your provider may choose to give certain vaccines subcutaneously even when the standard route is intramuscular. The concern is that an intramuscular injection could cause a hematoma (a pocket of blood) inside the muscle. Subcutaneous tissue is easier to compress after the injection, making it simpler to stop any bleeding.
This has been a longstanding practice, particularly for vaccines like tetanus. However, research has increasingly shown that intramuscular injection is safe for many anticoagulated patients when done with a fine needle and followed by firm pressure. Current CDC guidelines allow intramuscular injection of vaccines like tetanus-diphtheria on a case-by-case basis, even for patients on blood thinners. Your provider will weigh the specific vaccine, your medication, and your bleeding risk when choosing the route.
Common Injection Site Reactions
Subcutaneous injections can cause localized reactions at the injection site. Redness is the most frequent, followed by general soreness, pain, and itching. These reactions happen because the vaccine material sits in fatty tissue that drains slowly, keeping the immune-stimulating ingredients in contact with local tissue longer than a muscle injection would. Most injection site reactions are mild and resolve within a few days without treatment.
Compared to intramuscular shots, subcutaneous vaccines are somewhat more likely to cause a visible lump or firmness under the skin at the injection site. This is especially true if a vaccine meant for intramuscular delivery is accidentally given subcutaneously. For vaccines specifically designed for subcutaneous use, the formulations are optimized to minimize these effects.