Abstract: Introduction: Traumatic brain injury is the leading cause of death in children and adults in developed countries. Severe traumatic brain injury is classified with Glasgow Coma Scale score 8 and less. About 50% of patients with severe traumatic brain injury developes at least one infection as a complication of primary condition during hospitalization in the Intensive Care Unit, resulting with fatal outcome in 28% of patients. Ventilator — associated pneumonia is the leading infection that affects patients with severe traumatic brain injury, with an incidence between 41% and 74%. Following are sepsis and urinary tract infections. The aim: To analyze the number of patients with nosocomial infection and isolated severe traumatic brain injury hospitalized in the Intensive Care Unit of the Clinical Hospital Centre Rijeka, Croatia, from 31 st January 2013 to 31 st December 2014. Patients and methods: A two – year retrospective study included 46 patients with isolated severe traumatic brain injury and nosocomial infection hospitalized in the Intensive Care Unit of the Clinical Hospital Centre Rijeka,Croatia, in the period from 31 st January 2013 to 31 st December 2014. All medical data was collected from the Division of Intensive Care Unit, Clinical Hospital Centre Rijeka, Croatia. Results: From 67 patients with isolated severe traumatic brain injury, 46 (68,65%) of them developed nosocomial infection. There was statistically significant more male patients than female (p < 0.05). The average age of infected patients was 57,8 years. The leading were the infections of the respiratory system. Gram – negative bacteria Proteus mirabilis and Pseudomonas aerugnonsa were the leading pathogens. The average duration of the infection was 5,77 day. Duration of mechanical ventilation accounted for the majority of the patients more than 10 days. The average duration of treatment for all 46 patients was 10,475 days, and for 16 (34,78%) of them, the treatment outcome was lethal. Conclusion: Nosocomial infections are becoming a major public health problem. The emphasis must be set on the prevention which includes maintaining the hygiene and the antiseptic rules among the medical personnel of the Intensive Care Unit. Already developed infections must be adequately treated so the negative treatment outcomes can be reduced.