In order to evaluate the immunogenicity, safety and tolerability of influenza vaccination in children with inborn errors of metabolism (IEMs), we enrolled 20 patients with IEMs at risk of decompensation (14 males; mean age ± SD, 8.5 ± 3.9 years) and 20 healthy age- and gender-matched controls. Four weeks after vaccination, seroconversion rates were 75–85% and seroprotection rates 85–95%, with high geometric mean titers (GMTs) of all three influenza antigen strains in both groups. Three months after vaccination, most of the subjects remained seroconverted with high seroprotection rates and high GMTs for all the three influenza strains. Safety and tolerability were also very good, with no differences between the groups.