Intervention for individuals with autism spectrum disorder (ASD) typically commences after diagnosis.

No trial of an intervention administered to infants before diagnosis has shown an effect on diagnostic outcomes to date.

We determine the efficacy of a preemptive intervention for ASD beginning during the prodromal period.

This 2-site, single rater–blinded randomized clinical trial of a preemptive intervention vs usual care was conducted at 2 Australian research centers (Perth, Melbourne).

Community sampling was used to recruit 104 infants aged 9 to 14 months showing early behaviors associated with later ASD, as measured by the Social Attention and Communication Surveillance–Revised.

Recruitment occurred from June 9, 2016, to March 30, 2018. Final follow-up data were collected on April 15, 2020.

Infants were randomized on a 1:1 ratio to receive either a preemptive intervention plus usual care or usual care only over a 5-month period.

The preemptive intervention group received a 10-session social communication intervention, iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care comprised services delivered by community clinicians.