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Children with autism spectrum disorder (ASD) are often placed in inclusive mainstream education (ME) or exclusive special education (SE) settings. While ME settings usually offer less-intensive and structured intervention programs than SE settings, they offer more exposure to typically developing peers. A total of 121 children (2–5 years old) with ASD, 85 in SE and 36 in ME, completed two Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) assessments. Repeated-measures analysis of covariance (ANCOVA) analyses were used to assess longitudinal changes in ADOS-2 calibrated severity scores (CSS) and language production (estimated from the ADOS-2), while accounting for baseline cognitive scores, age of diagnosis, and parent-reported intensity of intervention. Longitudinal changes in ADOS CSS did not differ significantly across educational settings but were strongly associated with the age of diagnosis, demonstrating that children diagnosed earlier improved more regardless of educational settings. These findings suggest that children with ASD placed in SE and ME exhibit similar longitudinal changes in core ASD symptoms. Further studies comparing additional outcome measures such as cognitive abilities and adaptive behaviors are highly warranted for establishing placement recommendations and public health policies. Today, children with autism spectrum disorder (ASD) are placed in mainstream or special education settings somewhat arbitrarily with no clear clinical recommendations. Here, we compared changes in core ASD symptoms, as measured by the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) clinical assessment, across ASD preschool children placed in special or mainstream education. Longitudinal changes in ADOS-2 scores did not differ significantly across settings over a 1- to 2-year period. While some children improved in core ASD symptoms, others deteriorated in both settings. This highlights the need to identify specific criteria for establishing meaningful placement recommendations. [ABSTRACT FROM AUTHOR]