OBJECTIVES: Paediatric advisory committee guidelines recommend palivizumab prophylaxis for infants at high risk for respiratory syncytial virus (RSV) infection. The objective of this study is to compare the hospitalization rates for respiratory illness (RIH) and RSV-positive hospitalizations (RSVH) among infants who received palivizumab for various indications. METHODS: The Canadian Registry for Synagis (CARESS) is a prospective registry of infants who have received ≥1 dose of palivizumab per RSV season across Canada. Demographic data were collected in 32 Canadian national sites during the 2005-2012 RSV seasons. Respiratory illness related hospitalization events were recorded monthly. Standard risk indications that qualified for RSV prophylaxis were categorized as prematurity (≤35 completed weeks gestational age), chronic lung disease or bronchopulmonary dysplasia (CLD), hemodynamically significant congenital heart disease (CHD), and other serious underlying medical disorders (MD). A Cox proportional hazards analysis was conducted to examine differences in hospitalization rates between the indications.  RESULTS: Of the 13,310 infants enrolled, 8751 were premature, 1048 had CLD, 1414 had CHD, and 2097 qualified with MDs. The overall RIH rate was 6.6% (n=875) with premature infants having a significantly lower rate than the other groups (4.4% vs. 12.2% [CLD], 10.3% [CHD], 10.3% [MD]; B=-0.770, df=1, p<0.0005). Details of hospitalizations did not differ between groups, except the number that were admitted to the Intensive Care Unit which was significantly different between groups (χ2=11.420, df=3, p=0.010). The overall RSVH rate was 1.55% but was also significantly lower for prematurity (prematurity, 1.36%; CLD, 1.64%; CHD, 2.05%; MD, 2.03%; p<0.0005), with no significant differences between the groups in terms of time to RSV hospitalization (χ2=1.833, df=3, p= 0.608). CONCLUSIONS: RIH and RSVH rates were dissimilar across the groups with premature infants being significantly lower compared to the others. However there were no identified group differences regarding time to first RSVH.