Objective: School-age children with attention-deficit/hyperactivity disorder (ADHD) have reduced health-related quality of life (HRQoL), but it is unclear whether this is also true for preschool children. It is unknown whether parent training (PT) improves HRQoL. This study compared HRQoL in preschool children with ADHD with age-matched children from the general population; examined whether PT improves HRQoL; and tested if treatment-related changes in HRQoL were mediated by improvements in ADHD, parent efficacy, and family stress. Method: Parents of 164 children age 3–7 years with an ADHD diagnosis participated in a randomized controlled trial comparing the New Forest Parenting Programme and treatment as usual. Measures of HRQoL, ADHD, parent efficacy, and family stress were completed at baseline, posttreatment, and 36-week follow-up. Child baseline HRQoL was compared with two general population-based reference groups. PT effects were analyzed using linear models and mediation analyses. Results: Preschoolers with ADHD had lower HRQoL than the reference groups. The New Forest Parenting Programme, but not treatment as usual, was associated with improvement in psychosocial HRQoL at posttreatment (change 2.28, 95% CI [0.78, 3.77]) and at 36-week follow-up (change 2.05, 95% CI [0.56, 3.54]). This difference between treatment arms was not statistically significant. Parent efficacy and family stress scores at posttreatment significantly mediated improvements in HRQoL at 36-week follow-up; ADHD scores at posttreatment did not. Conclusion: ADHD negatively impacts HRQoL in early childhood. PT for ADHD has the potential to improve HRQoL independently of its effects on ADHD symptoms. Clinical trial registration information: A Controlled Study of Parent Training in the Treatment of ADHD in Young Children (D'SNAPP); http://clinicaltrial.gov/; NCT01684644.