Background: We evaluated the clinical outcomes and prognostic factors of patients requiring prolonged mechanical ventilation (PMV), defined as ventilator care for ${geq}21$ days, who were admitted to the medical intensive care unit (ICU) of a university hospital in Korea. Methods: During the study period, a total of 2,644 patients were admitted to the medical ICU, and 136 patients (5.1%) were enrolled between 2005 and 2010. Results: The mean age of the patients was $61.3{pm}14.5$ years, and 94 (69.1%) were male. The ICU and six-month cumulative mortality rates were 45.6 and 58.8%, respectively. There were 96 patients with tracheostomy placement after admission and their mean period from admission to the day of tracheostomy was $21.3{pm}8.4$ days. Sixty-three patients (46.3%) were successfully weaned from ventilator care. Of the ICU survivors (n=74), 34 patients (45.9%) were transferred to other hospitals (not university hospitals). Two variables (thrombocytopenia [hazard ratio (HR), 1.964; 95% confidence interval (CI), 1.225~3.148; p=0.005] and the requirement for vasopressors [HR, 1.822; 95% CI, 1.111~2.986; p=0.017] on day 21) were found to be independent factors of survival on based on the Cox proportional hazard model. Conclusion: We found that patients requiring PMV had high six-month cumulative mortality rates, and that two clinical variables (measured on day 21), thrombocytopenia and requirement for vasopressors, may be associated with prognostic indicators.