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Measles, mumps and rubella (MMR) still determine significant morbidity and mortality, although a highly effective vaccine is available. Postponing the MMR vaccination until 6 months after the last red blood cell (RBC) transfusion is recommended, but this delay is incompatible with chronic transfusions. The present study aimed at investigating the impact of blood transfusions on the immunogenicity of the MMR vaccine. In this observational study, a group of 45 transfusion- dependent (TD) patients was compared to 24 non-transfusion-dependent (NTD) patients. Immunity to measles was achieved in 35 (78%) TD and 21 (88%) NTD subjects (p = 0.7), to mumps in 36 (80%) TD and 21 (88%) NTD subjects (p = 0.99), and to rubella in 40 (89%) TD and 23 (96%) NTD subjects (p = 0.99). No significant difference was observed in the number of non-immune individuals or those with doubtful protection between the two groups (p &gt, 0.05). The mean IgG value, assayed in 50 pre-storage leukoreduced RBC units, was 0.075 ± 0.064 mg/mL, ten times lower than the level assumed in blood units and considered detrimental to the immune response in TD patients. This work shows a favorable response to MMR vaccination in TD and NTDT patients and paves the way for further larger studies assessing the impact of chronic transfusions on vaccine response.