From 2020 Personal, Social, Health and Economic Education will be compulsory in UK schools for adolescents, however less is known about how it can be taught in a an effective manner. We examine, through a randomised trial, the impact of an evidenced based health related quality of life (HRQoL) curriculum called Healthy Minds that ran in 34 high schools in England over a four-year period. We find robust evidence that Healthy Minds positively augments many physical health domains of treated adolescents. We also find some evidence that Healthy Minds positively affects behaviour, but has no impact on emotional wellbeing. We find notable gender effects, strongly favouring boys. We also present evidence that Healthy Minds changes career aspirations, with those exposed to treatment being less likely to choose competitive work and more likely to choose work that involves “people-skills”. Overall our work illustrates the potential for later childhood interventions to promote HRQoL and develop the career aspirations of adolescents.