OBJECTIVES: The objective of the study was to assess the effect of changes in health-related behaviours on academic achievement and on HRQOL of children and adolescents aged 8 – 18 years in a 3 years follow-up study. METHODS: A representative sample of Spanish children and adolescents aged 8-18 years participating in the KIDSCREEN follow-up study completed the self-administered HRQOL questionnaire KIDSCREEN-27, and questions regarding smoking and drinking habits (binge drinking), among others at baseline (2003) and 3 years after (2006). Academic achievement, a scale of the Child Health and Illness Profile (CHIP), was collected at follow-up. Data on gender and family socio-economic status was also collected. Multivariate linear regression analysis was performed to assess the influence of changes in health-related behaviours on academic achievement and HRQOL controlling for socioeconomic and family factors. RESULTS: Response rate at follow-up was 54% (n=454). Twenty six percent of the sample reported ever use of tobacco, while 4.6% reported to have started or to be a current regular smoker at follow-up; 18% reported starting or increasing alcohol consumption, and 16.5% on substance consumption (mainly cannabis). Preliminary multivariate analyses show that becoming a current smoker during the follow-up period was associated to worse Academic achievement among girls (beta coefficient=-5.0; p= 0.02); reporting ever drug consumption was associated with worse Psychological well-being among girls (beta= -3.1; p=0.04), and with worse Physical well-being among boys (beta= -5.9; p=0.004), at the follow-up. CONCLUSIONS: Changes in health-related behaviours are associated with worse outcome at 3 years of follow-up. Future studies should analyse factors related to susceptibility for regular use of tobacco and other drugs. Policy initiatives, and other factors should be taken into account preventing tobacco and other substance use at these ages.