Purpose <p>To improve the quality of aerosol delivery to infants, the iDP-ADS was advanced to include dual-prong nose-to-lung aerosol administration with a bifurcating interface, consistently monitor lung pressures and control ventilatory parameters with a pressure monitoring and control (PMC) unit, and implement flexible nasal prongs for use across a range of subject sizes.</p> Methods <p>Four bifurcating flow pathways were integrated into the iDP-ADS and tested <i>in vitro</i> with a full-term infant nose-throat (NT) model for comparison to the performance of a single-prong interface. After selecting the best-performing flow pathway, flexible prong designs were evaluated in the same model and chosen for additional testing. Realistic pulmonary mechanics (PM) and age-appropriate tidal volumes were used to simulate ventilation with the PMC unit and aerosol delivery in full-term and 34-week gestational age preterm NT models.</p> Results <p>Three of the four bifurcating flow pathways matched the performance of the single-prong design (tracheal filter delivery of ~55%), and the FP4 design with co-flow was selected. A flexible prong version of FP4 produced similar performance to the rigid version. Measurements from the PMC unit demonstrated that consistent air volumes under safe operating pressures could be delivered with a PEEP between 4–6 cmH₂O. Considering aerosol delivery, PM conditions resulted in ~4% decrease in filter deposition but high lung delivery efficiencies of ~45% and ~34% for the full-term and preterm models, respectively.</p> Conclusions <p>The best-performing interface with flexible prongs matched the lung delivery efficiency of a high-transmission single-prong interface and delivered high aerosol doses through late-preterm to full-term NT models.</p>