AimThe aim of this study was to investigate the status and effects of vitamin D supplement as adjuvant therapy in the management of respiratory distress syndrome (RDS) in preterm infants.Patient and MethodsVitamin D was prospectively studied in 196 preterm neonates, 96 of them developed RDS, which further subdivided into three subgroups (subgroup received just conventional therapy, subgroup received conventional therapy plus vitamin D 400 IU/day, and subgroup received conventional therapy plus vitamin D 800 IU/day). The patient selection for each treatment subgroup was done by computed randomization, and all the patients had the same treatment protocols assigned for each subgroup.ResultsThe preterm group who developed RDS had lower vitamin D concentrations than the preterm group without RDS (*P < .001). Also, the subgroups supplemented with vitamin D had lower Downes Respiratory Distress score and PaCO2 levels, less duration of hospitalization, and complications rates than the subgroup without vitamin D supplementation. The subgroup supplemented with 800 IU/day vitamin D showed also significantly improvement, less hospitalization duration, and less complications than those supplemented with 400 IU/day.Conclusions25‐hydroxyvitamin D concentration was deficient in most preterm babies especially those who developed RDS. Administration of 800 IU/day vitamin D as an adjuvant therapy in cases of RDS was associated with significant decreased in severity, rate of complications, and duration of hospital stay in preterm neonates with RDS.