Background: The management practices of Respiratory Distress Syndrome (RDS) in the newborn have changed over time. We examine the trends in the epidemiology, resource utilization, and outcomes (mortality and bronchopulmonary dysplasia [BPD]) of RDS in preterm neonates ≤34 weeks gestational age (GA) in the United States.Methods: In this retrospective serial cross-sectional study, we used ICD-9 codes to classify preterm infants GA ≤34 weeks between 2003 and 2014 from the National Inpatient Sample as having RDS or not. Trends in the prevalence of infants defined as RDS by ICD-9 code (ICD9-RDS), length of stay, BPD, and mortality were analyzed using Cochran-Armitage and Jonckheere-Terpstra tests and multivariable logistic regression.Results: Of 1 526 186 preterm live births with GA ≤34 weeks, 554 409 had ICD9-RDS (260 cases per 1000 live births) with the prevalence increasing from 170 to 361 (P trend < 0.001) and associated decrease in all-cause mortality (7.6% to 6.1%; P trend < 0.001) from 2003 to 2014. Increased utilization of non-invasive mechanical ventilation (NIMV) (69.5% to 74.3%; P trend < 0.001) was associated with decreased invasive mechanical ventilation (IMV) use >96 h (60.4 to 56.6%; P trend < 0.001). Exclusive NIMV use increased from 16.8% to 29.1% (P trend < 0.0001). BPD incidence decreased from 14% to 12.5% (P trend < 0.001). LOS increased from 32 days to 38 days (P trend < 0.001) and cost increased from $49,521 to $55,394 (P trend < 0.001).Conclusion: From 2003 to 2014, the assigned ICD9-RDS diagnosis, and utilization of NIMV increased and mortality among infants assigned the ICD9-RDS diagnosis decreased. With higher survival, hospital cost increased incrementally, indicating the importance of ongoing analysis of appropriate reimbursement for the care provided at tertiary centers for preterm infants. K E Y W O R D S bronchopulmonary dysplasia, epidemiology, invasive mechanical ventilation, national inpatient sample, non-invasive mechanical ventilation, respiratory distress syndrome Abbreviation: AHRQ, agency for healthcare research and quality; BPD, bronchopulmonary dysplasia; CI, confidence interval; HCUP, healthcare cost and utilization project; ICD-9-CM, International Classification of Diseases, Ninth edition, clinical modification; IMV, invasive positive pressure ventilation; NIMV, non-invasive mechanical ventilation; NIS, national inpatient sample; PN, preterm neonates; RDS, respiratory distress syndrome; TTN, transient tachypnea of the newborn.This study was presented in part as a poster abstract at the