Comfort measures, such as distraction (e.g., playing music or pretending to blow away the pain), ingestion of sweet liquids, use of pacifier, breast feeding, cooling of the injection site, and topical or oral analgesia, can help infants or children cope with the discomfort associated with vaccination. Pretreatment (30-60 minutes before injection) application of 5% topical lidocaine-prilocaine emulsion can decrease the pain of vaccination by causing superficial anesthesia. Topical lidocaine-prilocaine emulsion should not be used for infants who are receiving treatment with methemoglobin-inducing agents. Use of a topical refrigerant (vapocoolant) spray immediately before vaccination can reduce the short-term pain associated with injections and can be as effective as lidocaine-prilocaine cream. Administration of multiple injections simultaneously rather than sequentially also helps in reduction of pain. Use of the correct size needle and the correct site also reduces procedural pain and so does the application of pressure at the site of injection. Withdrawing the plunger after insertion to check for blood in the syringe prolongs the process of injection and is no longer recommended.

One study indicates that acetaminophen or ibuprofen used immediately and for 24 hours following DTwP vaccination reduces fever, discomfort and pain following vaccination in young infants. There is no evidence to suggest that using these agents prophylactically following DTwP in older children, or DTaP or other vaccines at any age is of any help in reducing post vaccination pain.