Respiratory syncytial virus (RSV) may cause severe illness in cystic fibrosis (CF) children, but recommendations vary on prophylaxis. CARESS is a prospective registry of children who received palivizumab in 32 Canadian sites from 2005 to 2016. Demographic data were collected at enrollment and respiratory illness-related events recorded monthly. We reviewed respiratory illness hospitalization (RIH) and RSV hospitalization (RSVH) in CF children aged < 24 months versus those prophylaxed for standard indications (SI; prematurity, chronic lung disease [CLD] and congenital heart disease [CHD]), and complex medical disorders (CM). Of 23,228 children analyzed, 19,452 (83.8%) were SI, 3349 (14.4%) were CM, and 427 (1.8%) were CF. CF children were more likely to be Caucasian, heavier at birth and enrollment, and less likely to have a sibling or live in crowded conditions. CF children were similar to the other groups in daycare attendance, history of atopy, and exposure to smoking. RIH incidences were 4.3% (premature), 13.8% CLD, 11.5% CHD, 11.7% CM, and 6.8% CF. RSVH incidence in CF children was similar to that in the SI and CM groups: 1.1, 1.5, and 2.0% groups respectively. Cox regression analyses showed that compared to CF children, the HRs for RSVH in SI (HR 2.0 95% CI 0.5–8.3, p = 0.3) and CM (HR 2.4, 95% CI 0.6–9.8, p = 0.2) did not differ. CF children are equally at risk for RSVH relative to those prophylaxed for other indications. Pending robust evidence from prospective trials, palivizumab could perhaps be considered in the interim, for young CF patients born early during the RSV season with evidence of serious lung disease.