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BACKGROUND: Patients undergoing prolonged mechanical ventilation represent up to 15% of all patients requiring weaning from mechanical ventilation. Although recent guidelines have recommended including physiotherapy early during mechanical ventilation to speed the process of weaning, only indirect evidence supporting the use of physiotherapy is available for patients receiving prolonged mechanical ventilation. The aim of our study was to evaluate the effects of a physiotherapy program in subjects requiring prolonged mechanical ventilation and the correlates of successful weaning. METHODS: A retrospective analysis was performed on 1,313 consecutive patients admitted to a weaning unit over a 15-y period to be liberated from prolonged mechanical ventilation. Subjects underwent a program of intensive physiotherapy organized in 4 incremental steps (1–4) and were analyzed according to the steps achieved (> 2 steps or ≤ 2 steps). The rate of successful weaning was recorded, and possible predictors were considered. The 15-y period of observation was divided into 3 consecutive 5-y intervals. RESULTS: Out of 560 subjects undergoing final analysis, 349 (62.3%) were successfully weaned. The weaning success rate was significantly greater in subjects attaining > 2 steps than in subjects who attained ≤ 2 steps (72.1% vs 55.9%, respectively, odds ratio = 2.04, 95% CI = 1.42–2.96, P 2 physiotherapy steps was the main predictor of successful weaning (odds ratio = 2.17, 95% CI = 1.48–3.23, P