Introduction: the preterm birth is a risk factor for child developmental and behavioral problems. Objective: to examine whether neonatal clinical characteristics of infants born preterm, as well as temperament assessed in toddlerhood, predict behavior problems during the preschool years. Methods: twenty-one children born preterm with very low birth weight were assessed longitudinally at three different ages: in the neonatal period, during toddlerhood, and in preschool. Medical charts were reviewed to assess infants' clinical illness characteristics at the neonatal phase. Mothers fulfilled the Early Childhood Behavior Questionnaire for assessing temperament at the toddlerhood and the Child Behavior Checklist-1.5-5 for assessing children's behavior problems at the preschool age. Results: very low birth weight associated with child temperament at the toddlerhood predicted behavior problems at the preschool age. High levels of excitement about expected pleasurable activities as well as low levels of inhibitory control increased the chance of exhibiting externalizing behavior problems. Otherwise, high levels of both gross and fine motor activation increased the chance of exhibiting internalizing behavior problems. Conclusion: prematurity associated with temperament of poor self-regulation in developmental processes comprises a multiple-risk condition for clinical behavior problems in the preschool age.