The aims of this study were to investigate the outcomes of patients requiring prolonged mechanical ventilation (PMV) and to identify risk factors associated with its mortality rate. All patients admitted to the respiratory care centre (RCC) who required PMV (the use of MV ≥21 days) between January 2006 and December 2014 were enrolled. A total of 1,821 patients were identified; their mean age was 69.8 ± 14.2 years, and 521 patients (28.6%) were aged >80 years. Upon RCC admission, the APACHE II scores were 16.5 ± 6.3, and 1,311 (72.0%) patients had at least one comorbidity. Pulmonary infection was the most common diagnosis (n = 770, 42.3%). A total of 320 patients died during hospitalization, and the in-hospital mortality rate was 17.6%. A multivariate stepwise logistic regression analysis indicated that patients were more likely to die if they who were >80 years of age, had lower albumin levels (<2 g/dl) and higher APACHE II scores (≥15), required haemodialysis, or had a comorbidity. In conclusion, the in-hospital mortality for patients requiring PMV in our study was 17%, and mortality was associated with disease severity, hypoalbuminaemia, haemodialysis, and an older age.