OBJECTIVES: To examine whether there is a difference in the incidence of maternal and perinatal risk factors, the incidence of comorbidities preterm infants and hypotrophic neonates with and without respiratory distress syndrome (RDS), and to analyze clinical apperaeance and relevant vital signs, and also to evaluate outcomes of the RDS. STUDY DESIGN: A cross-sectional study with historical data. PARTICIPANTS AND METHODS: The study was conducted at the Clinic of Pediatrics, University Hospital Centre Osijek, in neonates with birth-weight under 2500 grams and gestational age below 37 weeks that have been born beetween 1. 1. 2018. and 31. 12. 2019. 533 infants were included in the study. Data were collected from medical records: basic demographic data on mother, pregnancy, predisposing prenatal and neonatal risk factors and comorbidities, corticosteroid prophylaxis, surfactant application and respiratory support, early laboratory parameters and clinical characteristics of infants with RDS. RESULTS: RDS was developed in 193 infants (36,2 %). Maternal thrombocytopenia, anemia, preeclampsia, genitourinary infections and gynecological diseases as well as maternal medication-taking action such as use of antibiotics, antyhipertensives, gestagens and tokolytics are significant maternal risk factors for developing RDS. Significant perinatal risk factors are anhydramnios, placental abruption, prolapse of the umbilicus or amniotic fluid, SIAI, PRVP, MSAF and perinatal asphyxia. Neonates with shorter gestational age, lower birth weight, Apgar score and caesarian section type of delivery were significantly more likely to develop RDS. The occurrence of irregular respiration, pneumothorax and bronchopulmonary dysplasia, the development of sepsis and the presence of comorbidities such as ASD, BPD, DAP and intracranial hemorhage are risk factors for the development of RDS. Early laboratory parameters prove significant acidosis and hyponatremia in predicting the risk of developing RDS. Half of children with RDS received a surfactant and were significantly more likely to be on non invasive / invasive MV and oxygenotherapy with longer stays on non-invasive MV and higher doses of O2. CONCLUSION: RDS occurs in preterm infants and hypotrophic neonates as a combination of different risk factors (maternal, perinatal) and various forms of comorbidities that are characteristic for preterm infants and hypotrophic neonates.