Introduction: Multi-Drug Resistance (MDR) is defined as acquired resistance to at least one agent in three or more antimicrobial groups. The impact of multidrug-resistant (MDR) organisms in pediatrics is increasing globally. This study aimed to identify the frequency and clinical impact of Multidrug-resistant bacteria in pediatric and neonatal intensive care units in Zagazig University Hospital. Methods: The present study was a cross sectional study conducted in pediatric and neonatal intensive care units, pediatric department, Zagazig University children hospital in period between January 2019 to July 2019 on 150 cases (males and females) of critically ill infants, and children. Full history, clinical examination, and full laboratory tests were taken such as complete blood count (CBC), C reactive protein (CRP). Microbiological techniques: cultures were done to samples from different sites that included: blood, urine, and tracheal aspirate. Statistical analysis was done for these data. Results: The most common resistant organisms were Gram negative bacteria like: klebsiella pneumoniae, its resistance rate was (24.3%), followed by pseudomonas aeruginosa with resistance rate (19.5%). Staph epidermidis was the most prevalent Gram positive bacteria, its rate was (11.3%), and most of these bacteria were non multi drug resistant. Conclusion: The risk factors for acquisition of MDR bacteria in this study were: mechanical ventilation, prolonged hospital stay, CVC, and excessive use of antibiotics. MDR bacteria resulted in prolonged hospital stay and elevated mortality rate more than non MDR bacteria.