OBJECTIVES: To understand current management (utilization, compliance) with palivizumab prophylaxis of children at high-risk of RSV infection in Canada. METHODS: A prospective, observational, registry of infants at high risk for RSV who received at least one dose of palivizumab during the 2006 to 2008 RSV seasons from 24 sites. Neonatal and demographic data were collected upon enrollment. Data on palivizumab utilization and compliance, including outcomes related to a respiratory infection were collected monthly until the full course of palivizumab was completed or at the end of the relevant RSV season. RESULTS: A total of 2910 infants were enrolled, age two days to 47 months (mean=5.5 months). In total, 54.4% were male, 62.2% Caucasian, average gestational age (GA) was 32.0±6.8 completed weeks. 2079 (71.4%) infants received palivizumab because they were premature only (i.e. ≤35 completed weeks GA), 255 (8.8%) required oxygen, 288 (9.9%) had congenital heart disease and 288 (9.9%) were prophylaxed for other risk factors such as CNS disorders, airway anomalies and cystic fibrosis. Compliance was high; 77.8% received at least four injections of palivizumab between September and June each season. Overall 12, 973 doses were given. No directly related serious adverse events were identified. A total of 159 infants had 194 hospitalizations for respiratory tract infections (hospitalization rate 5.5%) and rates were highest in those with chronic lung disease (9.8%, p=0.006). The RSV positive hospitalization rate was only 0.96%. CONCLUSIONS: The RSV hospitalization rate observed in the 2006-2008 RSV seasons was lower than that found in several published reports (range1.3%-5.3%).The rates of RSV hospitalization may be decreasing for various reasons such as high compliance with palivizumab prophylaxis, variability in RSV epidemiology, hospital admission criteria and preventive education.