OBJECTIVES: To examine the pattern of palivizumab utilization and compliance in infants with pre-existing disease within the Canadian Registry Database (CARESS) METHODS: A prospective, registry of infants across 27 sites who received at least 1 dose of palivizumab during the 2006-2009 RSV seasons. Neonatal and demographic data were collected from the parent/caregiver at enrollment. Data on palivizumab utilization, compliance, and outcomes related to respiratory illness (RI) events were collected monthly. Premature infants ≤35 completed weeks gestational age without medical conditions who met standard approval criteria for palivizumab (Group 1) were compared to those with underlying medical disorders who received prophylaxis (Group 2). RESULTS:  Group 1 (n=3379) Group 2 (n=489). Male: 56.8% versus 54.6% (P=0.433). Average Enrollment Age (months) ± SD: 3.6 ± 3.4 versus 9.9 ± 8.8 (P=0.000). Average GA (weeks) Mean ± SD: 31.0 ± 3.1 versus 37.1 ± 4.3 (P=0.000). Average # injections ± SD: 3.6 ± 1.5 versus 3.7 ± 1.5 (P=0.159). Hospitalization Rate (HR) for RI: 4.1% versus 9.2% (P=0.000). RSV HR: 1.3% versus 2.7% (P<0.05). On average infants received 86.0% ± 28.3% of the expected number of injections. Group 2 infants comprised Down syndrome (n=118, 24.1%), upper airway anomalies (n=112, 22.9%), cystic fibrosis (n=62, 12.7%), neuromuscular impairment (n=42, 8.6%), pulmonary (n=38, 7.8%), multiple system disorders (n=34, 7.0%), cardiac (n=17, 3.5%), immunocompromise (n=8, 1.6%), and miscellaneous (n=58, 11.9%). From 2006-2009, the proportion of Group 2 infants receiving prophylaxis increased 2-fold from 5.6% (69/1224) to12.2% (245/2016).  Overall. Group 2 infants were older at enrollment with more advanced GA and had significantly higher RI and RSV hospitalization rates. No serious adverse events directly related to palivizumab occurred. CONCLUSIONS:  Results imply that infants with underlying medical disorders that are not approved for prophylaxis by advisory bodies and current position statements are at greater risk for RSV infections and hospitalization.