BACKGROUND: Caregivers of children with attention-deficit/hyperactivity disorder (ADHD) experience more parenting stress than do caregivers of children without ADHD. Evidence suggests that ADHD severity is positively associated with parenting stress. In adolescents, ADHD increases the risks of contracting Coronavirus disease 2019 (COVID-19) and having poor outcomes. This follow-up study explored the prospective and cross-sectional factors influencing parenting difficulties experienced by the caregivers of adolescents with ADHD during the COVID-19 pandemic. METHODS: The following data were collected at baseline (before the outbreak of the pandemic in Taiwan): caregivers' demographic characteristics, affiliate stigma, parenting stress, depressive and anxiety symptoms, perceived ADHD causes, and adolescents' ADHD, oppositional defiant disorder (ODD), depressive, and anxiety symptoms. The following data were collected at follow-up (after the pandemic): caregivers' parenting difficulties during the pandemic, depressive and anxiety symptoms, and adolescents' ADHD symptoms. RESULTS: Stepwise multivariate regression analysis indicated that caregivers' parenting stress and adolescents' hyperactivity and impulsivity symptoms at baseline were positively correlated with caregivers' parenting difficulties during the pandemic. Furthermore, adolescents' hyperactivity, impulsivity, and ODD symptoms at follow-up were cross-sectionally and positively correlated with caregivers' parenting difficulties during the pandemic. CONCLUSION: Caregivers' parenting stress and adolescents' hyperactivity, impulsivity, and ODD symptoms should be considered when developing interventions for improving caregivers' ability to manage adolescents with ADHD, particularly in relation to self-protection, learning, life changes, daily routines, and emotional well-being.