Abstract Background: Respiratory distress syndrome of neonates (RDS) is one of the most common causes of neonatal mortality. Objective: The purpose of this study was to investigate socio-demographic, maternal and neonatal factors related to RDS in neonates in context of tertiary level hospital. Methods: This cross sectional study was conducted in Dhaka Medical College Hospital and Ad-din Women’s Medical College and Hospitalduring 1 st January to 31 December 2017 among 186 purposively selected neonates. Data were collected by document review and face to face interview with complete privacy using semi-structured questionnaire and check list. Results: Regarding socio-demographic factors, Considering the maternal factors, majority of the mothers(61.3%) had taken 4 or more checkup during their antenatal period and 87.1% had institutional delivery while approximately half (52.7%) of the mothers had Caesarean delivery. Among the mothers, 17.2% had history of high blood pressure during pregnancy, 10.8% diabetes mellitus, 14% oligohydramnios and 37.1% mothers had PROM. RDS was more common in preterm neonates or below 37 weeks (85.5%) and maximum were low birth weight or below 2500 gram (90.3%), 52 babies (28%) were born of multiple pregnancy, more than half of the babies (62.4%) had moaning sound (grunting) and most of all (92.5%) had chest recession. Conclusion: The factors related to RDS are not preventable but are predictable if ANC for all the mothers can be ensured.If the possibility of occurrence of RDS can be assumed considering these factors, necessary precautions for earlier diagnosis and adequate management can be taken which can contribute in reducing neonatal mortality rate. Keywords: Respiratory distress syndrome, neonatal mortality, intercostals recession, intercostals recession.