This study explored North Carolina pediatric healthcare professional’s (PHP) perceptions of screening 12–18 month old infants for Autism Spectrum Disorder (ASD). Eight focus groups (66 PHPs) were conducted across practice settings. The purpose was to explore PHP’s perspectives to: inform development of ASD screening tools and ultimately impact their use in PHP settings. PHPs reported concerns, barriers, and the need for research to support early ASD screening. Additionally, they expressed the need for: (a) clear “red flags” of ASD for 12–18 month olds; (b) socioculturally sensitive and effective screening tools; (c) effective early interventions; (d) systems to handle potential increases in referrals; and (e) continuing education. PHPs also demonstrated preferences about screening tool characteristics and processes for enhancing screening efforts.