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Background and Objectives: Systems of care emphasize parent-delivered intervention for children with autism spectrum disorder (ASD). Meanwhile, multiple studies document psychological distress within these parents. This pilot longitudinal randomized controlled trial compared the parent-implemented Early Start Denver Model (P-ESDM) to P-ESDM plus mindfulness-based stress reduction (MBSR) for parents. We evaluated changes in parent functioning during active treatment and at follow-up., Methods: Participants included children (<36 months old) with autism spectrum disorder and caregivers. Participants were randomly assigned to P-ESDM only ( n = 31) or P-ESDM plus MBSR ( n = 30). Data were collected at baseline, midtreatment, the end of treatment, and 1, 3, and 6 months posttreatment. Multilevel models with discontinuous slopes were used to test for group differences in outcome changes over time., Results: Both groups improved during active treatment in all subdomains of parent stress (β = -1.42, -1.25, -0.92; P < 0.001), depressive symptoms, and anxiety symptoms (β = -0.62 and -0.78, respectively; P < 0.05). Parents who received MBSR had greater improvements than those receiving P-ESDM only in parental distress and parent-child dysfunctional interactions (β = -1.91 and -1.38, respectively; P < 0.01). Groups differed in change in mindfulness during treatment (β = 3.15; P < .05), with P-ESDM plus MBSR increasing and P-ESDM declining. Treatment group did not significantly predict change in depressive symptoms, anxiety symptoms, or life satisfaction. Differences emerged on the basis of parent sex, child age, and child behavior problems., Conclusions: Results suggest that manualized, low-intensity stress-reduction strategies may have long-term impacts on parent stress. Limitations and future directions are described., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)