BACKGROUND: In addition to clinical measures in the evaluation of paediatric interventions, health related quality of life (HRQoL) is an important outcome. The TAPQOL (TNO-AZL Preschool children Quality of Life) was developed to measure HRQoL in preschool children. It is a generic instrument consisting of 12 scales that cover the domains physical, social, cognitive, and emotional functioning. AIMS: To evaluate the feasibility, score distribution, internal consistency, test-retest reliability, and discriminative and concurrent validity of the TAPQOL multi-item scales in preschool children, aged 2-48 months. Also to evaluate the feasibility, reliability, and validity separately for infants (2-12 months old) and toddlers (12-48 months old). METHODS: Parents of a random general population sample of 500 preschool children were sent a questionnaire by mail. A random subgroup of 159 parents who participated received a retest after two weeks. RESULTS: The response rate was 83% at the test and 75% at the retest. There were few missing answers. Six scales showed ceiling effects. Nine scales had Cronbach's alphas >0.70. In general, score distributions and Cronbach's alphas were comparable for infants and toddlers. Test-retest showed no significant differences in mean scale scores; two scales had intra-class correlations <0.50. Five scales showed significant differences between children with no conditions versus children with two or more parent reported chronic conditions. CONCLUSION: Results showed that the TAPQOL is a feasible instrument to measure HRQoL and support the reliability and discriminative validity of the majority of its scales for infants as well as toddlers.