INTRODUCTION: Implementation of a weaning protocol is related to better patient prognosis. However, new approaches may take several years to become the standard of care in daily practice. We conducted a prospective cohort study to investigate the effectiveness of a multifaceted strategy to implement a protocol to wean patients from mechanical ventilation (MV) and to evaluate the weaning success rate as well as practitioner adherence to the protocol. METHODS: We investigated all consecutive MV-dependent subjects admitted to a medical-surgical intensive care unit (ICU) for >24h over 7years. The multifaceted strategy consisted of continuing education of attending physicians and ICU staff and regular feedback regarding patient outcomes. The study was conducted in three phases: protocol development, protocol and multifaceted strategy implementation, and protocol monitoring. Data regarding weaning outcomes and physician adherence to the weaning protocol were collected during all phases. RESULTS: We enrolled 2469 subjects over 7years, with 1,943 subjects (78.7%) experiencing weaning success. Physician adherence to the protocol increased during the years of protocol and multifaceted strategy implementation (from 38% to 86%, p<0.01) and decreased in the protocol monitoring phase (from 73.9% to 50.0%, p<0.01). However, during the study years, the weaning success of all subjects increased (from 73.1% to 85.4%, p<0.001). When the weaning protocol was evaluated step-by-step, we found high adherence for noninvasive ventilation use (95%) and weaning predictor measurement (91%) and lower adherence for control of fluid balance (57%) and daily interruption of sedation (24%). Weaning success was higher in patients who had undergone the weaning protocol compared to those who had undergone weaning based in clinical practice (85.6% vs. 67.7%, p<0.001). CONCLUSIONS: A multifaceted strategy consisting of continuing education and regular feedback can increase physician adherence to a weaning protocol for mechanical ventilation.