Due to current increase in the rate of nosocomial infections, our objective was to examine the frequency, risk factors, clinical presentation and etiology of nosocomial infections in patients with central nervous system infections. 2246 patients with central nervous system infections, treated in the intensive care units of the Institute of Infectious and Tropical Diseases, Clinical Center of Serbia in Belgrade and at the Department of Infectious Diseases of the Clinical Hospital Center Kragujevac, were included in this retrospective and prospective study. Clinical manifestations of nosocomial infections were registered in 180 (12.7%) patients. Direct risk factors for nosocomial infections were: venous lines, urinary catheter, length of stay over 20 days, inhibitors of gastric secretion, consciousness disorders and coma, endotracheal intubation, tracheotomy and controlled ventilation for 5 days or more. The most frequent clinical presentations of nosocomial infections were: tract urinary infections, bacteriemia/sepsis and nosocomial pneumonia. Significantly higher frequency of death outcomes was registered in patients with nosocomial infections.