Objective: To determine palivizumab utilization in infants with pre-existing disease within the Canadian Registry Database (CARESS).Methods: A prospective registry of infants from 27 sites who received palivizumab during the 2006-2009 RSV seasons. Demographic data were collected from the parent/caregiver at enrollment. Data on palivizumab utilization, compliance, and outcomes related to respiratory infection (RI) events were collected monthly. Infants ≤35 weeks gestational age (GA) who met current approval criteria (Group 1) were compared to those with medical disorders who received off-label palivizumab (Group 2).Results: Group 1 (n=3379) Group 2 (n=489). Male: 56.9% vs 54.9% (P=0.43). Average Enrollment Age (months) ± SD:3.6 ± 3.4 vs 9.9 ± 8.8 (P=0.00). Average GA (weeks) Mean ± SD: 31.0 ± 3.1 vs 37.1 ± 4.3 (P=0.00). Average # injections ± SD:3.6 ± 1.5 vs 3.7 ± 1.5 (P=0.16). Hospitalization Rate (HR) for RI:4.1% vs 9.2% (P=0.00). RSV HR: 1.0% vs 2.2% (P=0.04). Compliant injections: 67.6% vs 67.6% (P=0.99)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%). The proportion of Group 2 infants receiving prophylaxis increased from 5.6% (69/1224) to12.2% (245/2016). Group 2 infants were older at enrollment with more advanced GA and had significantly higher RI and RSV hospitalization rates.Conclusion: Clinicians strongly advocate for palivizumab in special populations based on perceived morbidity and mortality risk and evolving evidence from small cohort and case-controlled studies.