Purpose: This study was aimed to examine the effectiveness of early intervention for very low birth weight (VLBW, birth weight <1,500 g) preterm infants in mother-infant feeding interaction at 4 and 6 months corrected age. Methods: This study enrolled 62 term infants and 179 VLBW infants that the latter were randomly assigned into usual care program (UCP), clinic-based intervention program (CBIP) and home-based intervention (HBIP) group. Mother-infant dyads feeding activity were examined using the Assessment of Mother Infant Sensitivity- Chinese version (AMIS-C). Infants’ heart rate variability (HRV) was assessed using an electrocardiography at 4 and 6 months corrected age. Results: For interactive behavior, the CBIP group showed significantly higher maternal scores on the AMIS-C than the HBIP at 4 and 6 months corrected age (p = 0.004); whereas, the infant, dyadic and total scores of all groups were comparable. As for the physiological response, all groups showed similar HRV at baseline and during feeding at 6 months corrected age. Furthermore, a higher AMIS-C dyadic and total score on at 4 months were associated with a smaller change in some HRV indices from baseline to feeding at 6 months in all groups (all r=-0.16, p<0.05). A higher AMIS-C maternal and total score on at 6 months was each associated with a smaller change in some HRV indices from baseline to feeding at 6 months (r=-0.20 to -0.16, all p<0.05). Conclusion: VLBW preterm dyads showed comparable interactive behavior and infant’s heart rate variable than term dyads during feeding at 4 and 6 months corrected age. Early intervention delivered at clinic visit was more beneficial than that delivered at home in altering maternal feeding behavior during the follow-up period.