Objective To characterise the effects of early and exclusive enteral nutrition with either maternal or donor milk in infants born very preterm (28^0/7–32^6/7 weeks of gestation).

Design Parallel-group, unmasked randomised controlled trial.

Setting Regional, tertiary neonatal intensive care unit.

Participants 102 infants born very preterm between 2021 and 2022 (51 in each group).

Intervention Infants randomised to the intervention group received 60–80 mL/kg/day within the first 36 hours after birth. Infants randomised to the control group received 20–30 mL/kg/day (standard trophic feeding volumes).

Main outcome measures The primary outcome was the number of full enteral feeding days (>150 mL/kg/day) in the first 28 days after birth. Secondary outcomes included growth and body composition at the end of the first two postnatal weeks, and length of hospitalisation.

Results The mean birth weight was 1477 g (SD: 334). Half of the infants were male, and 44% were black. Early and exclusive enteral nutrition increased the number of full enteral feeding days (+2; 0–2 days; p=0.004), the fat-free mass-for-age z-scores at postnatal day 14 (+0.5; 0.1–1.0; p=0.02) and the length-for-age z-scores at the time of hospital discharge (+0.6; 0.2–1.0; p=0.002). Hospitalisation costs differed between groups (mean difference favouring the intervention group: −$28 754; −$647 to −$56 861; p=0.04).

Conclusions In infants born very preterm, early and exclusive enteral nutrition increases the number of full enteral feeding days. This feeding practice may also improve fat-free mass accretion, increase length and reduce hospitalisation costs.

Trial registration number NCT04337710.