In this study, we investigated how the birth of a very low birth weight preterm (VLBW) infant influences the mother-infant interaction at 3 months. We also focused on the impact of the infant's neurobiological risk and maternal anxiety, and their interaction. The comparison of the VLBW preterm sample (n = 79) with an external full-term sample (n = 35) showed mother-infant interactions of the families with the preterm infant to be more vocally responsive during the interaction, but less facially responsive during the interaction. Additionally, higher levels of maternal anxiety were associated with preterm infants being less facially responsive in interaction with their mother. While neurobiological risk of the infant played a part in this association, with higher risk infants also being less facially responsive, the relationship with maternal anxiety and the mother-child interaction was stronger. How these findings may influence therapeutic interventions is discussed.