INTRODUCTION: The aim of the study was to determine whether the use of a nurses' protocol-directed weaning procedure, based on the French intensive care society (SRLF) consensus recommendations, was associated with reductions in the duration of mechanical ventilation and intensive care unit (ICU) length of stay in patients requiring more than 48 hours of mechanical ventilation. METHODS: This prospective study was conducted in a university hospital ICU from January 2002 through to February 2003. A total of 104 patients who had been ventilated for more than 48 hours and were weaned from mechanical ventilation using a nurses' protocol-directed procedure (cases) were compared with a 1:1 matched historical control group who underwent conventional physician-directed weaning (between 1999 and 2001). Duration of ventilation and length of ICU stay, rate of unsuccessful extubation and rate of ventilator-associated pneumonia were compared between cases and controls. RESULTS: The duration of mechanical ventilation (16.6 +/- 13 days versus 22.5 +/- 21 days; P = 0.02) and ICU length of stay (21.6 +/- 14.3 days versus 27.6 +/- 21.7 days; P = 0.02) were lower among patients who underwent the nurses' protocol-directed weaning than among control individuals. Ventilator-associated pneumonia, ventilator discontinuation failure rates and ICU mortality were similar between the two groups. DISCUSSION: Application of the nurses' protocol-directed weaning procedure described here is safe and promotes significant outcome benefits in patients who require more than 48 hours of mechanical ventilation.