Although many parameters were investigated about weaning and mortality in critical patients in intensive units, no studies have yet investigated predictors in prolonged mechanical ventilation (PMV) patients following successful weaning. A cohort of 142 consecutive PMV patients with successful weaning in our respiratory care center was enrolled in this study. Successful weaning is defined as a patient having smooth respiration for more than 5 days after weaning. The results showed as follows: twenty-seven patients (19%) had the reinstitution within 14 days, and 115 patients (81%) had the reinstitution beyond 14 days. Renal disease RIFLE-LE was associated with the reinstitution within 14 days (P = 0.006). One year mortality rates showed significant difference between the two groups (85.2% in the reinstitution within 14 days group versus 53.1% in the reinstitution beyond 14 days; P < 0.001). Kaplan-Meier analysis showed that age ≥70 years (P = 0.04), ESRD (P = 0.02), and the reinstitution within 14 days (P < 0.001) were associated with one-year mortality. Cox proportional hazards regression model showed that only the reinstitution within 14 days was the independent predictor for mortality (P < 0.001). In conclusion, the reinstitution within 14 days was a poor predictor for PMV patients after successful weaning.