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Background: This study was conducted to examine the hypothesis that a tracheostomy prior to admission to a respiratory care center (RCC) with a specialized weaning setting would improve the outcome of patients transferred from intensive care unit previously maintained on prolonged mechanical ventilation. Methods: A retrospective review of medical records from intubated adult patients admitted to the Chi-Mei Medical Center, a 16-bed RCC in Southern Taiwan from January 1, 2001 through July 31, 2012, was performed. The outcomes at weaning (without ventilator support within 120 hours), mortality, and expenditure at hospital discharge were compared between the tracheostomy group (n = 1216) and the endotracheal tube group (n = 1187), and the predictors of weaning in all patients were determined. Results: The overall weaning rate and the in-hospital mortality rate were 68.2% and 16.4%, respectively. The tracheostomy group showed significantly higher weaning rate and shorter hospital stay (73.5% vs. 62.8% and 57.4 vs. 61.0 days, both p < 0.01) compared with the endotracheal tube group. In-hospital mortality, total ventilator days, and cost of hospitalization were comparable between groups. Factors predictive of successful weaning were surgical origin [odds ratio (OR) 2.165], higher albumin (OR 1.937), tracheostomy group (OR 1.543), higher PaO2/fraction of inspired oxygen (OR 1.345), and lower blood urea nitrogen (OR 0.984). Conclusion: Tracheostomy creation prior to RCC admission was associated with a significantly higher weaning rate and reduced hospital stays. The provision of assessment of the aforementioned markers may be helpful in the clinical setting to facilitate the optimal management and the accreditation of medical care quality of patients with prolonged mechanical ventilation.