Background. This prospective cohort study was done to identify determinants of successful weaning from mechanical ventilation among patients admitted to the 10-bed long-term ventilator unit (LTVU) of a teaching hospital. Methods. Prospective patient surveillance and data collection were done on 472 patients admitted to the LTVU over a 4-year period (January 1996 to December 1999). Results. Multiple logistic regression analysis showed that the absence of home mechanical ventilation at the time of hospital admission, absence of intensive care unit (ICU) readmission, and admission to the LTVU from a nonmedical service were independently associated with successful weaning. No statistical difference between hospital survivors and nonsurvivors was associated with length of stay in the LTVU and length of stay in the hospital. Conclusions. Patients admitted to an LTVU require prolonged hospitalizations and intensive resource utilization. These data suggest that improved methods for identifying patients who are unlikely to benefit from prolonged mechanical ventilation may assist physicians in their discussions with patients and family members as they consider various treatment options.