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This prospective longitudinal study examined prediction models of quality of life (QoL) in preterm-born individuals at preschool age by considering predictors factors from the neonatal phase (clinical, socioeconomic, and neurobehavioral variables), the first year (developmental variables), and preschool age (clinical, socioeconomic, developmental, and functional variables). The neurobehavioral performance of 24 low-risk preterm-born children was evaluated before reaching term. Psychomotor development was evaluated during their first year. At 5 years, preschoolers’ functionality was assessed and the Child Health Questionnaire-50 Parent Form was used to assess child’s QoL from the perspective of their parents. Children displayed deficits in 7 of 15 domains of the QoL measure. Prediction models indicated that the children’s lower QoL values were associated with the following risk factors: sexually transmitted disease in the mother during gestation, male gender, lengthy hospitalization period after birth, use of corticotherapy, poor alertness and orientation in the neonatal phase, risk in motor development at 4–6 months, respiratory disease, use of medications, history of severe accidents, risk in personal–social behavior, poor social function at preschool age, and low socioeconomic status. In conclusion, the QoL in low-risk preterm children at preschool age could be affected by clinical and developmental risk factors. Thus, the multiple risk factors should be examined in preventive follow-up programs of premature infants.