OBJECTIVES: To compare palivizumab utilization and compliance in infants who meet standard indications for RSV prophylaxis versus those with pre-existing medical disorders within the Canadian Registry Database (CARESS). METHODS: A prospective, observational registry of infants across 29 sites who received at least 1 dose of palivizumab during the 2006-2010 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 (GA) without medical conditions who met standard approval criteria for palivizumab (Group 1) were compared to infants with underlying medical illnesses (Group 2). RESULTS: 5832 patients were analyzed (Group 1, n=4880; Group 2, n=952). The two groups were similar in terms of gender (male: 56.4% versus 55.6%; p=0.829). Group 2 infants included Down syndrome (n=193, 20.3%), upper airway anomalies (n=178, 18.7%), pulmonary disorders (n=127, 13.3%), cystic fibrosis (n=117, 12.3%), neuromuscular impairment (n=78, 8.2%), multiple system disorders (n=57, 6.0%), cardiac disorders (n=22, 2.3%), immunocompromise (n=17, 1.8%), and miscellaneous (n=163, 17.1%). From 2006-2010, the proportion of Group 2 infants receiving prophylaxis increased 3.4-fold from 5.6% (69/1224) to 19.1% (462/2413). Overall, Group 2 infants were older at enrollment (10.2 ± 9.2 versus 3.5 ± 3.1 months, p<0.005), had a significantly higher GA (35.9 ± 6.0 versus 31.0 ± 5.4 completed weeks, p<0.005) and had significantly higher RI (9.0% versus 4.2%, p<0.0 05) and RSV hospitalization (2.35% versus 1.32%, p=0.003) rates. A lower proportion of Group 2 infants were compliant with treatment (69.4% versus 72.6%, p=0.048). There were no serious adverse events directly related to palivizumab. CONCLUSIONS: Results imply that infants with underlying medical disorders that are not specifically approved for prophylaxis by advisory bodies and current position statements are at significant risk for hospitalization with respiratory illness and RSV infections and may benefit from immunization.