Mechanical ventilation increases the frequency of nosocomial infections. This study describes the frequency of multi-resistant viridans streptococcal colonisation, the clinical course of nosocomial sepsis and ventilator-associated pneumonia in mechanically ventilated neonates in the neonatal intensive care unit of Ankara University Hospital. Seventy-nine ventilated newborns were enrolled. Broncho-alveolar lavage culture and blood cultures were positive in 44 (56%) and 17 (22%) patients, respectively. The most predominant micro-organisms in broncho-alveolar lavage cultures were multi-resistant viridans streptococci (29, 66%). Viridans streptococci were also one of the predominant organisms in blood cultures (5/17, 29%). In 29 patients with broncho-alveolar lavage positive for viridans streptococci, nine (31%) had colonisation, 15 (52%) had ventilator-associated pneumonia and five (17%) had sepsis owing to viridans streptococcus. Ventilator-associated pneumonia was encountered in 52/1000 ventilation days. Mortality was caused by infection in three (10%) of them. Mechanically ventilated neonates in our neonatal intensive care unit had a high rate of both multi-resistant viridans streptococcus airway colonisation and subsequent ventilator-associated pneumonia and sepsis.