Background Weaning and extubation follow each other in clinical practice, and are two isolated processes that pose distinct problems. Extubation failure is the need for reinstitution of ventilatory support within 24 to 72 hours of planned removal of endotracheal tube. Nearly 20% of patients require reintubation. Reintubation is more serious and may be associated with more adverse effect than the initial intubation procedure. Patients needing reintubation had significantly increase the duration of mechanical ventilation as well as ICU, hospital stay and mortality. Objective of the study To predict risk factors of reintubation in respiratory patients. Patients and methods The present study was a prospective observational study. It involved 100 mechanically ventilated patients who were admitted to RICU with different respiratory diseases. All patients met the criteria for readiness to wean: 50 patients need to be reintubated (group 1), and the other 50 patients were successfully extubated without needing for reintubation within 48–72 hours of extubation process (group 2). Different clinical, laboratory analysis, hemodynamic and respiratory variables, ventilator parameter and SAPS II score were collected in both groups. Results The mean age of reintubated patients was (66.06±10.3 years) and most of them were males (58%). We found that heamoglobin level (11.4±1.93) and Albumin level (2.47±0.61 g/dl) were significantly lower in reintubated group. Also, PH (7.11±0.032) and PaO2 (38.3±4.85 mmHg) at time of first intubation were significantly lower in reintubated cases. Half (50%) of reintubated cases expressed difficult weaning. On the other hand, 64% in non reintubated patients expressed simple weaning. Age (≥64 years old), PH (≤7.13), PaO2 (≤45) at first intubation, SAPS II Score, hemoglobin level (≤10.1), albumin level (≤3.1) were independent predictors of reintubation in respiratory ICU patients. Conclusion Age, arterial PH, PaO2 at first intubation, SAPS II Score, hemoglobin, albumin, higher length of ICU stay and hospital stay were an independent predictors of reintubation in respiratory ICU patients.