Abstract Background Infants born at 33–35 completed weeks’ gestational age (wGA) aged <6 months at the start of or born during respiratory syncytial virus (RSV) season and classified as moderate/high risk of severe RSV disease were included in a palivizumab RSV prophylaxis program in the province of Quebec, Canada, until 2014–2015. We assessed the impact of withdrawal of this indication on lower respiratory tract infection (LRTI)/RSV hospitalizations (H) in this population. Methods We conducted a 4-year, retrospective, cohort study in 25 Quebec hospitals (2 seasons with and 2 without palivizumab prophylaxis for moderate- to high-risk infants). Our primary outcome was LRTI/RSV-H incidence. We compared LRTI/RSV-H incidence before (2013–2015; seasons 1 + 2 [S1/2]) and after (2015–2017; S3/4) the change in indication. Results We identified 6457 33–35 wGA births. LRTI/RSV-H occurred in 105/3353 infants (3.13%) in S1/2 and 130/3104 (4.19%) in S3/4. Among LRTI/RSV-H, 86.4% were laboratory-confirmed RSV-H. Adjusting for sex, wGA, and birth month, S3/4 was significantly associated with increased LRTI/RSV-H incidence (adjusted odds ratio [aOR], 1.36; 95% confidence interval [CI], 1.04–1.76) but not with laboratory-confirmed RSV-H (aOR, 1.19; 95% CI, 0.90–1.58). Mean duration of LRTI/RSV-H was 5.6 days; 22.6% required intensive care unit admission. Comparing S3/4 with S1/2, infant percentage with LRTI/RSV-H classified as moderate/high risk increased from 27.8% to 41.9% (P = .11). Conclusions In a province-wide study, we observed a significant increase in LRTI/RSV-H incidence among infants born at 33–35 wGA in the 2 years after withdrawal of RSV prophylaxis.