BackgroundIdentifying mechanisms of change in Autism treatment may help explain response variability and maximize efficacy. For this, the child-therapist interaction could have a key role as stressed by developmental models of intervention, but still remains under-investigated. AimsThe longitudinal study of treatment response trajectories considering both baseline and child-therapist interaction features by means of predictive modeling. Methods and ProceduresN = 25 preschool children were monitored for one year during Naturalistic Developmental Behavioral Intervention. N = 100 video-recorded sessions were annotated with an observational coding system at four time points, to extract quantitative interaction features. Outcomes and ResultsBaseline and interaction variables were combined to predict response trajectories at one year, and achieved the best predictive performance. The baseline developmental gap, therapist’s efficacy in child engagement, respecting children’s timing after fast behavioral synchronization, and modulating the interplay to prevent child withdrawal emerged as key factors. Further, changes in interaction patterns in the early phase of the intervention were predictive of the overall response to treatment. Conclusions and ImplicationsClinical implications are discussed, stressing the importance of promoting emotional self-regulation during intervention and the possible relevance of the first period of intervention for later response.