The Modified Checklist for Autism in Toddlers (M-CHAT) and the Early Screening of Autistic Traits (ESAT) were designed to screen for autism spectrum disorders in very young children. The aim of this study was to explore proportions of children that screened positive on the ESAT or the M-CHAT and to investigate if screening positive on the ESAT and M-CHAT is associated with clinical referral by 18 months and other aspects of children’s development, health, and behavior. In this study, the mothers of 12,948 18-month-old children returned a questionnaire consisting of items from the ESAT and M-CHAT, plus questions about clinical and developmental characteristics. The M-CHAT identified more screen-positive children than the ESAT, but the ESAT was associated with more clinical referrals and tended to identify more children with medical, language, and behavioral problems. A post hoc analysis of combining the two instruments found this to be more effective than the individual instruments alone in identifying children referred to clinical services at 18 months. Further analysis at the level of single items is warranted to improve these screening instruments.