Background and purpose: Drug interaction (DI) decreases the success rate of treatments and lead to longer hospitalization and increased treatment cost. Also, it can seriously endanger patient's lives or cause many complications. The purpose of this study was to evaluate the incidence and management of drug interactions in neonatal intensive critical care unit (NICU) in a teaching hospital. Materials and methods: This cross-sectional descriptive study was performed in 50 neonates admitted to Sari Bu-Ali Sina NICU, 2013-2014. Patients’ data and parameters related to drugs were recorded. Results: Drug interactions were observed in 21 patients. From 1131 prescriptions DIs appeared in 386 cases. The mean number of DIs in each neonate was 3.5±1.6 and most of them occurred in patients concurrently receiving 5 to 10 drugs per day. Conclusion: The majority of neonates in NICU have critical conditions and need multiple therapies so it is necessary to conduct some interventions such as determination of serum concentration, dose adjustment and laboratory parameters monitoring.