AIMS/HYPOTHESIS: The aim of our study was to assess the associations of serum alpha- and gamma-tocopherol concentrations with the risk of advanced beta cell autoimmunity in children with HLA-conferred genetic susceptibility to type 1 diabetes mellitus. METHODS: A case-control study with 108 cases with advanced beta cell autoimmunity and 216 matched control participants nested within the birth cohort of the Type 1 Diabetes Prediction and Prevention Project. A serum sample for vitamin E analyses was collected from all the children in the cohort at the age of 1 year and thereafter at 12 month intervals. For each case-control group, all the repeated serum samples up to the age of seroconversion to autoantibody positivity in the case were analysed. A conditional logistic regression model was used to determine potential associations between seroconversion and serum tocopherol concentrations. RESULTS: Serum alpha- or gamma-tocopherol concentrations were not significantly associated with the risk of advanced beta cell autoimmunity. The odds ratio (95% CI) for micromol/l increase in serum concentration of the first-year sample was 0.97 (0.92-1.03) for alpha-tocopherol and 1.10 (0.70-1.74) for gamma-tocopherol. However, there was an interaction between high values of gamma-tocopherol at the age of 1 year and the time of seroconversion (p = 0.024). CONCLUSIONS/INTERPRETATION: It seems unlikely that high concentrations of alpha- or gamma-tocopherol protect against advanced beta cell autoimmunity in young children.