Although maternal antenatal transfer is the preferred option, some infants inevitably need urgent transport to a tertiary neonatal care facility after birth. This study aimed to investigate trends over time in patient characteristics and respiratory management in a large series of neonatal emergency transfers, in order to provide health caregivers an up-to-date profile of such patients and their therapeutic needs. Trends in patient characteristics and respiratory management were evaluated in 3337 transfers by the Eastern Veneto Neonatal Emergency Transport Service in 2000–2019. Joinpoint regression analysis was performed to evaluate trends and to estimate annual percentage changes (APCs). Proportions of preterm neonates increased (APC 2000–2012 2.25%), then decreased (APC 2012–2019 − 6.04%). Transfers at birth increased (APC 2000–2013 2.69%), then decreased (APC 2013–2019 − 5.76%). Proportion of neonates with cardiac and surgical diseases declined (APCs 2000–2019 − 6.82% and − 3.32%), while proportion of neonates with neurologic diseases increased (APC 2000–2019 8.62%). Use of nasal-continuous-positive-airway-pressure (APC 2000–2019 9.72%) and high-flow-nasal-cannula (APC 2007–2019 58.51%) at call, and nasal-continuous-positive-airway-pressure (APC 2000–2019 13.87%) and nasal-intermittent-mandatory-ventilation (APC 2000–2019 32.46%) during transfer increased. Mechanical ventilation during transfer decreased (APC 2014–2019 − 10.77%). Use of oxygen concentrations at 21% increased at call and during transfer (APCs 2000–2019 2.24% and 2.44%), while oxygen concentrations above 40% decreased at call and during transfer (APCs 2000–2019 − 3.93% and − 5.12%). Conclusion : Our findings revealed a shift toward a more “gentle” approach and the reduced use of oxygen in respiratory management. Equipment and team expertise should meet the requirements of such changing patients and their therapeutic needs. What is Known: • Although antenatal transfer is the preferred option, some infants inevitably need urgent transport to a tertiary neonatal care facility after birth. • Trend studies investigating cohort information with appropriate statistical methods represent useful instruments to detect changes over time. What is New: • Our findings revealed marked changes in patient characteristics and respiratory management in a large series of neonatal emergency transfers during the last two decades. • Equipment and team expertise should meet the requirements of such changing patients and their therapeutic needs.