Preterm infants are at risk for developing altered trajectories of cognitive, social, and linguistic competences compared to a term population. This is mainly due to medical and envi- ronmental factors, as they are exposed to an atypical auditory environment and simultaneously, long periods of early separation from their parents. The short-term effects of early vocal contact (EVC) on an infant's early stability have been investigated. However, there is limited evidence of its impact on the infant's autonomic nervous system maturation, as indexed by heart rate variability, and its long-term impact on infant neurodevelopment. Our multi-centric study aims to investigate the effects of EVC on a preterm infant's physiology, neurobehaviour, and development. Eighty stable preterm infants, born at 25–32 weeks and 6 days gestational age, without specific abnormalities, will be enrolled and randomised to either an intervention or control group. The intervention group will receive EVC, where mothers will talk and sing to their infants for 10 min three times per week for 2 weeks. Mothers in the control group will be encouraged to spend the same amount of time next to the incubator and observe the infant's behaviour through a standard cluster of indicators. Infants will be assessed at baseline; the end of the intervention; term equivalent age; and 3, 6, 12, and 24 months corrected age, with a battery of physiological, neurobehavioral, and developmental measures. Early interventions in the neonatal intensive care unit have demonstrated effects on the neurodevelopment of preterm infants, thereby lowering the negative long-term effects of an atypical auditory and interactional environment. Our proposed study will provide new insight into mother–infant early contact as a protective intervention against the sequelae of prematurity during this sensitive period of development. Early intervention, such as EVC, is intuitive and easy to implement in the daily care of preterm infants. However, its long-term effects on infant neurodevelopment and maternal sensitivity and stress are still unclear.