This study examined the effects and mediators of a clinic-based intervention program (CBIP) and a home-based intervention program (HBIP) compared with usual care in very-low-birth-weight (VLBW) preterm infants on developmental and behavioral outcomes at 24 months of age (corrected for prematurity). In this randomized controlled trial, VLBW preterm infants received either CBIP (n=57), HBIP (n=63), or usual care (n=58) from hospitalization to 12 months. At 12 months, infant emotional regulation was assessed using the toy-behind-barrier procedure and dyadic interaction was observed during free play. At 24 months, infant developmental and behavioral outcomes were assessed using the Bayley Scales of Infant and Toddler Development- 3rd edition and the Child Behavior Checklist for Ages 1.5-5, respectively. Compared with infants under usual care, the CBIP-group infants showed higher cognitive composite scores (difference, 95% confidence interval (CI)=4.4, 0.8-7.9) and a lower rate of motor delay (odds ratio (OR), 95% CI=0.29, 0.08-0.99); the HBIP-group infants had lower sleep problem scores (difference, 95% CI=-1.4, -2.5 to -0.3) and a lower rate of internalizing problems at 24 months (OR, 95% CI=0.51, 0.28-0.93) (all p<.05). The CBIP's effect on cognitive outcome was attenuated when maternal or dyadic interactive behavior was considered; whereas the HBIP's effect on sleep and internalizing behavior was attenuated when duration of orientation to a toy or object was considered. In conclusions, interventions enhanced the cognitive, motor, and behavioral outcomes of VLBW preterm infants. The effects on cognitive and behavioral outcomes might be mediated by early-improved mother-infant interaction and infant emotional regulation, respectively.