We examined predictors of mental health difficulties and wellbeing in caregivers of children with autism in the Pre-school Autism Communication Trial cohort in middle childhood (N = 104). Child's intellectual disability, daily living skills impairment, elevated emotional and behavioural difficulties, high educational level of caregiver and household income below the median significantly predicted caregivers' mental health difficulties, but autism severity, child communication skills and family circumstances did not. Lower caregiver mental wellbeing was predicted by elevated child emotional and behavioural difficulties. The need to support the mental health and wellbeing of caregivers of children with autism is discussed in light of the results.