Background Despite ongoing improvements in clinical care, preterm infants experience a variety of stressors in the first weeks of life, including necessary medical procedures, which may affect development. Some stress-reduction programmes based in the Neonatal Intensive Care Unit (NICU) have reported a positive impact on development. In particular, trials of the Mother-Infant Transaction Program (MITP) have shown positive short and longer term effects, and are based on training parents to recognise and minimise stress responses in preterm infants. Aims To evaluate the impact on early developmental milestones of an enhanced MITP (PremieStart) delivered over an extended period in the NICU. Study design This was a parallel 2-group randomised controlled trial involving 109 women with 123 infants born at < 30 weeks gestation assessed initially at term-equivalent age and then at 6 months' corrected-age. Results Intervention mothers were more sensitive in providing infant care, stressed their infants less, showed greater awareness of, and responded more appropriately to, negative infant cues (p < 0.05 in each case). Intervention infants displayed significantly lower stress when being bathed by mothers at term-equivalent age (p < 0.05). At 6 months corrected-age, intervention infants showed higher mean scores on the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist. The strongest effects appeared in Symbolic behaviour (p = 0.05) and this was reflected in the Total score (p < 0.05). Conclusions As significant cognitive and language deficits are reported in longitudinal studies of preterm children, an intervention that improves early infant communication abilities is promising, especially since previous research suggests that the strongest benefits may emerge at later ages.