IntroductionRespiratory distress syndrome is a catastrophic respiratory problem among low birth weight neonates. It increases the suffering of neonates and the economic expenditure of the countries. Notably, it is a major public health issue in low-income and middle-income countries such as Ethiopia. Despite this, studies regarding respiratory distress syndrome among low birth weight neonates were limited in Ethiopia.ObjectiveTo assess the incidence and predictors of respiratory distress syndrome among low birth weight neonates in the first 7 days in Northwest Ethiopia Comprehensive Specialized Hospitals.MethodMulticentred institution-based retrospective follow-up study was conducted from 19 September 2021 to 1 January 2023, among 423 low birthweight neonates. A simple random sampling technique was used. The data were collected using a data extraction checklist from the medical registry of neonates. The collected data were entered into EPI-DATA V.4.6.0.6. and analysed using STATA V.14. The Kaplan-Meier failure curve and log-rank test were employed. Bivariable and multivariable Weibull regression was carried out to identify predictors of respiratory distress syndrome. Statistical significance was declared at a p≤0.05.ResultThe incidence rate of respiratory distress syndrome was found to be 10.78 (95% CI 9.35 to 12.42) per 100 neonate days. Fifth minute Appearance, Pulse, Grimace, Activity, Respiration (APGAR score) <7 (AHR 1.86; 95% CI 1.18 to 2.92), multiple pregnancy (AHR 1.43; 95% CI 1.04 to 1.96), caesarean section delivery (AHR 0.62; 95% CI 0.41 to 0.93), prematurity (AHR 1.56; 95% CI 1.06 to 2.30) and birth weight <1000 g (AHR 3.14; 95% CI 1.81 to 5.40) and 1000–1499 g (AHR 2.06; 95% CI 1.42 to 2.83) were significant predictors.ConclusionThe incidence of respiratory distress syndrome was higher than other studies conducted on other groups of neonates. Multiple pregnancy, fifth minute APGAR score, caesarean section, prematurity, extremely low birth weight and very low birth weight were predictors of respiratory distress syndrome. However, it needs further prospective study. Therefore, the concerned stakeholders should give due attention and appropriate intervention for these predictors.