We investigated health-related quality of life in preterm children in association with birth weight, breastfeeding and maternal emotional state. A cross-sectional study was carried out involving 97 mothers of 2-year-old children born below 2500 g. Participants completed the Pediatric Quality of Life Inventory and a comprehensive psychological interview. Birth weight and chronic neonatal morbidities were not significant predictors of quality of life at 2 years. However, breastfeeding and positive maternal emotional state were important protective factors to the prospective quality of life of preterm children. Retrospectively, calm mothers reported their children more positively comparing to anxious mothers both during their pregnancy and after birth. As protective factors, the positive maternal emotional state before and after childbirth and breastfeeding are more crucial in the development of quality of life at 2 years than biological factors.