BACKGROUND Topical lidocaine 2.5% and prilocaine 2.5% (EMLA) is effective in decreasing the pain associated with minor procedures including immunization, although the effect on the antibody response to vaccine constituents has not been assessed. OBJECTIVE To measure the antibody response to measles-mumps-rubella (MMR) vaccine, as well as pain reduction associated with the use of the EMLA patch. METHODS One hundred sixty healthy infants at least 12 months old undergoing their first MM immunization in an ambulatory setting. METHODS Randomized, double-blind, controlled trial of EMLA patch (5%-1 g) or placebo before MMR immunization. Blood sampling before and 28 to 35 days after immunization. METHODS The primary outcome measure was the antibody response to measles by plaque reduction neutralization and to mumps and rubella by enzyme immunoassay. The secondary outcomes were pain scores by the Modified Behavioral Pain Scale and drug- and vaccine-associated adverse events. RESULTS There was no difference in the antibody response between the EMLA- and placebo-treated groups. The response rates in the EMLA group were 89.7%, 88.3%, and 92.3% to measles, mumps, and rubella, respectively, compared with rates of 91.1%, 94.9%, and 93.7% in the placebo group (P >.05 for all comparisons). EMLA recipients had less pain after immunization (mean Modified Behavioral Pain Scale score increase 3.1 compared with 3.8; P =.043) and less irritability (16% compared with 31%; P =.040) than did placebo recipients. CONCLUSIONS The EMLA patch has no adverse effect on the antibody response to MMR vaccine and significantly reduces the pain associated with the subcutaneous administration of the vaccine.