Rationale: Noninvasive ventilation (NIV) is the first-line therapy in infants with bronchiolitis-related acute respiratory failure. However, there is a lack of data regarding weaning from NIV in this setting. Working hypothesis: This study aims to evaluate a nurse-driven weaning protocol in this homogenous population. Study design: A retrospective single-center study with pre-versus-post comparative design in a tertiary center. Methodology: Data from all infants aged ≤ 6 months admitted to the PICU during 2 seasons with a clinical diagnosis of bronchiolitis and requiring any type of noninvasive ventilatory support on admission, were analyzed. Main results: In total, 187 infants (95 with standard and 92 with nurse-driven protocols) were included; the median age was 47 (IQR 24-75) and 31 days (19-58) in patients at baseline and after the protocol implementation, respectively. There was no difference in terms of weaning failure between the two periods (11 (12%) versus 14 (15%), p=0.46). At baseline, the ventilatory support duration was 70 hours (IQR 54-104) versus 56 hours (IQR 29-83) during the nurse-driven protocol period (p=0.29). The PICU and hospital lengths of stay did not differ between the two periods. No complication related to NIV occurred in the two periods. Conclusions: In patients with bronchiolitis supported by NIV, the nurse-driven weaning management - as opposed to physician-driven - was not associated with a significantly higher proportion of weaning failure cases.