IMPORTANCE Universal early screening for autism spectrum disorder (ASD) is recommended but not routinely performed. OBJECTIVE To determine whether computer-automated screening and clinical decision support can improve ASD screening rates in pediatric primary care practices. DESIGN, SETTING, AND PARTICIPANTS This cluster randomized clinical trial, conducted between November 16, 2010, and November 21, 2012, compared ASD screening rates among a random sample of 274 children aged 18 to 24 months in urban pediatric clinics of an inner-city county hospital system with or without an ASD screening module built into an existing decision support software system.