OBJECTIVES: Palivizumab is recommended for respiratory syncytial virus (RSV) prophylaxis. CARESS tracks palivizumab use and respiratory outcomes in high-risk infants, including those with congenital airway anomalies (CAA). Our objective was to compare hazards for hospitalization for respiratory illness (RIH) and RSV (RSVH) in CAA infants versus those prophylaxed for: 1) other medical disorders (MD) and 2) standard indications (SD). METHODS:  Infants were prospectively recruited from 32 Canadian sites who received ≥1 dose of palivizumab during the 2005-2012 RSV seasons.  Utilization and hospitalization outcomes were collected monthly throughout respective seasons. RESULTS: 13,310 infants were enrolled (309 CAA, 1816 MD, 11185 SD).  There were statistically significant group differences (p<0.05) in: enrolment and gestational age, birth and enrolment weight, proportions of: Caucasians, daycare attendance, smoking exposure, siblings, multiple birth, household crowding, and atopy. Compliance, calculated by inter-dose intervals, was similar across the groups - overall rate 73.2%.  CAA infants had a RIH rate of 12.9%; MD (9.9%); SD (5.9%) with significantly increased hazard of hospitalization compared to MD (HR = 1.47, 95%CI: 1.04-2.10, p = 0.030) and SD (HR = 1.92, 95%CI: 1.39-2.67, p <0.0005).  40/309 CAA infants were hospitalized for RI, 32 were tested for RSV; 4 were positive (RSVH rate: 1.61% versus 2.06% (MD), 1.47% (SD). By Cox proportional hazard analysis, CAA did not increase hazard of first RSVH compared to MD or SD infants (χ2 = 0.79, df = 2, p = 0.67). After risk factor adjustment for daycare attendance, siblings, smoking exposure and crowding, the model was significant (χ2 = 66.1, df = 10, p <0.0005); however, individual groups as risk factors remained insignificant (p = 0.73). CONCLUSIONS: This is the largest report of CAA infants who have received palivizumab world-wide. Despite differences in risk factors, the groups appear to have similar hazards in terms of RSVH.