Background: Children born very low birth weight (VLBW) are at increased risk for regulatory difficulties. However, identifying toddlers at risk has been impeded by a lack of screening measures appropriate for this population. Methods: We studied the nature of dysregulation in toddlers born VLBW (N = 32) using the Infant-Toddler Social and Emotional Assessment (ITSEA) Dysregulation Domain, a multiscale (including negative emotionality, sleep, eating, and sensory sensitivity) screening assessment of regulatory abilities. Results: As evidence of construct validity for this population, ITSEA scores for toddlers born VLBW showed greater overall dysregulation, as well as sensory sensitivity, compared with an ITSEA manual-­based premature/LBW sample. This was seen both by higher overall Dysregulation Domain scores and higher percentages of toddlers exceeding the clinical cutoff levels. Furthermore, compared with age­- and gender­-matched full-­term toddlers, the VLBW toddlers displayed gender-­specific dysregulation profiles. Conclusions: The greater overall dysregulation in VLBW toddlers compared with premature/LBW toddlers suggests that early screening for such difficulties among VLBW toddlers is warranted, and this study provides preliminary evidence that the ITSEA Dysregulation Domain may be an appropriate screening measure.