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Measles, mumps, and rubella (MMR) and varicella (V) vaccines are often coadministered at 1 clinic visit. This study (104389/NCT00127023) was undertaken to assess the immunogenicity and safety of a new refrigerator-stable tetravalent MMRV vaccine after 1 dose and after 2 doses administered during the second year of life.Nine hundred seventy healthy children aged 10–21 months received 2 doses of MMRV vaccine (Priorix-Tetra; GlaxoSmithKline Biologicals, Rixensart, Belgium) 42 days apart (MMRV group; N = 732) or 1 dose of MMR vaccine (Priorix) coadministered with varicella vaccine (Varilrix) followed by a second dose of only MMR vaccine 42 days later (MMR + V group; N = 238).Observed seroconversion rates for measles, mumps, rubella, and varicella antibodies 42 days postdose 1 were 94.5%, 96.1%, 99.7%, 95.5% in the MMRV group and 93.4%, 93.6%, 98.1%, 95.6% in the MMR + V group. Respective seroconversion rates postdose 2 were 98.3%, 99.4%, 99.7%, 99.7% in the MMRV group and 97.6%, 99.5%, 100%, 97.5% in the MMR + V group. Observed antimeasles and antimumps geometric mean titers (GMTs) were higher after each dose in the MMRV group than in the MMR + V group. Antivaricella GMT increased 21-fold in the MMRV group postdose 2, and was markedly higher than in the MMR + V group who did not receive a second dose of varicella (1903.3 and 80.3 dilution−1, respectively). Both vaccine regimens were generally well-tolerated in terms of local reactions, fever >39.5°C, and vaccine-related rashes.Both after 1 dose and after 2 doses, the MMRV vaccine was at least as immunogenic as concomitant MMR and varicella vaccination suggesting that it could be suitable for use according to current vaccination schedules.