Abstract The Royal Liverpool Children's Hospital—Alder Hey paediatric intensive care unit (PICU) usually has a low rate of nosocomial respiratory syncytial virus (RSV) infection. We report and analyse a major outbreak of nosocomial (acquired) RSV infection on the PICU during a RSV season. All children admitted to the PICU were studied during the six-month winter period 1 October 2002 to 31 March 2002. Nasopharyngeal aspirates were tested using an in vitro enzyme-linked immunoassay (ELISA) membrane test for RSV antigen. PICU-acquired RSV infection was considered to have occurred when a child admitted to the PICU was RSV negative, or from whom no samples were taken as they did not exhibit signs of bronchiolitis, but was RSV positive five or more days after the admission. Fifty-four patients tested RSV positive using the ELISA on the PICU. All the patients were ventilated. Thirty-nine children were RSV positive using the ELISA on admission to the PICU (‘imported’ cases) and 15 became RSV positive whilst on the PICU (‘acquired’ cases). The source of the acquired RSV infection accounting for the first peak/outbreak in nosocomial cases were RSV-positive children in isolation cubicles. Acquired cases of RSV infection subsided with reinforcement of traditional methods of barrier precautions. The source of the second peak in nosocomial cases were persistent shedders of RSV. Seventy-three percent (11/15) of the acquired RSV cases had one or more of the following co-morbidities: congenital heart disease, chronic lung disease, airways abnormalities or immunosuppression. Droplet precautions (strict handwashing, use of gloves if handling body fluids, single-use aprons, education) rather than the physical barrier of the cubicle itself played a more important role in curtailing nosocomial spread. Persistent shedders of RSV are an important potential source of nosocomial RSV infection within a PICU. Patients with co-morbidities are at increased risk of nosocomial RSV infection.