High negative reactivity in early childhood interferes with later academic and behavioral adjustment. Thus, investigating the origins of high negative affectivity in early childhood is of high relevance for understanding emotional morbidity after preterm birth. The present work explored (1) direct prematurity-related consequences for negative reactivity, (2) self-regulatory deficits as a mechanism indirectly relating prematurity to negative affectivity and (3) the implications of the interplay between procedural distress in the neonatal period and parenting stress for preterm children's negative reactivity. The sample was comprised of 146 preterm children (very vs. moderately to late preterm) and 86 healthy full-term children, both free of major neurological impairment. Assessment involved negative affect and parenting stress (parent-report; 12, 24 months corrected age, CA), effortful control (behavioral battery, parent report; 24 months CA) and the number of potentially distressing neonatal intensive care procedures as well as severity of illness during the neonatal period (retrospective chart review). There was no direct link from prematurity to a disposition for high negative reactivity in early childhood nor was prematurity indirectly associated with higher negative reactivity through lower levels of effortful control. The relation between neonatal pain and distress and negative affectivity depended on the level of parenting stress with low parenting stress at the end of the first year of children's life buffering the negative influence of neonatal distress. The present findings underscore the importance of complex interactions among environmental factors in processes of emotional plasticity after preterm birth thereby providing critical suggestions for follow-up care.