This study examines the construct validity of the First-Year Inventory 2.0 with respect to other established instruments in a sample of high-risk infant siblings of children with Autism Spectrum Disorder. The First-Year Inventory 2.0 is a parent-report screening instrument designed to identify 12-month-old infants at risk for an eventual diagnosis of Autism Spectrum Disorder and consists of two domains: Social-Communication and Sensory-Regulatory. Although the FirstYear Inventory 2.0's screening psychometrics have been examined, its construct validity has not been investigated. In a sample of 112 high-risk 12-month-olds, we examined the First-Year Inventory 2.0's associations with the Autism Observation Scale for Infants, an observer-based Autism Spectrum Disorder screener, and with other developmental instruments measuring similar areas in social communication and regulatory functioning in young children. Findings generally supported the First-Year Inventory 2.0 associations with other instruments in expected ways. The First-Year Inventory 2.0 Social-Communication domain was notably associated with the Autism Observation Scale for Infant's total score and with language and communication domains of the Vineland and the Mullen. The Sensory-Regulatory domain showed minimal associations with other instruments that only had a few sensory items. Considering different objectives and strengths of assessments, researchers and clinicians are encouraged to utilize a variety of instruments in a comprehensive evaluation of a child.