Neurobehavioral Disinhibition (ND) is a complex condition of psychological dysregulation reflecting a wide range of problems involving difficulties with emotion regulation. Respiratory Sinus Arrhythmia (RSA) is a physiological correlate of emotion regulation that has been studied in a variety of at-risk populations; however, there are no studies of RSA in children with ND. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included l 073 participants. Resting RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. ND was assessed at age 8/9, 11, and 13/100 years via behavioral dysregulation and poor executive functioning composite measures. Greater exposure to early adversity was related to increased behavioral dysregulation from age 8/9 to 13/14, less RSA reactivity at 3 years, and increases in RSA reactivity from age 3 to 6 years. A significant early adversity x RSA reactivity quadratic interaction revealed that children with decelerations in RSA reactivity exhibited increases in behavioral dysregulation, regardless of their exposure to early adversity. However, greater exposure to early adversity was related to greater increases in behavioral dysregulation, but only if children exhibited accelerations in RSA reactivity from age 3 to 6 years. Results contribute to our understanding of how interactions across multiple levels of analysis contribute to the development of ND.