RATIONALE: Extubation strategy for mechanically ventilated patients with Coronavirus Disease 19 is different from that for patients with other viral pneumonia. We reported 2 cases of Coronavirus Disease 19 receiving tracheal intubation twice during the hospitalization. PATIENT CONCERNS: Two elderly patients with onset of fever and upper respiratory tract infection were confirmed as Coronavirus Disease 19, 1 of whom had chronic obstructive pulmonary disease previously. With active antiviral and noninvasive respiratory supportive therapy, there was no improvement, thus mechanical ventilation (MV) was adopted. Combining with symptomatic and supportive treatment, their oxygenation recovered and then extubation was carried out. However, 96 hours later, they underwent endotracheal intubation again due to their Coronavirus Disease 19 progression. DIAGNOSIS: Critically ill Coronavirus Disease 19 requiring tracheal intubation owing to respiratory failure with lung.javascript. INTERVENTIONS: Initial Strategy for respiratory failure included endotracheal intubation, MV, antiviral treatment and cortisol in both cases. When extubation criteria were satisfied, early discontinuation of MV was conducted, then rehabilitation exercise and nutritional support followed. However, 96 hours later, the disease progressed leading to respiratory failure again, thus reintubation was performed. Later, veno-venous extracorporeal membrane oxygenation was performed owing to aggravation of respiratory failure, assisted by prone position treatment and sputum drainage, then status became stable and stepped into recovery stage. OUTCOMES: Both patients underwent reintubation, and their MV time and Intensive care unit residence time were prolonged. Through prone position treatment, sputum drainage and awake extracorporeal membrane oxygenation strategy, patient has been transferred to rehabilitation unit in Case 1, and patient in Case 2 has been in recovery stage as well with stable pulmonary status and was expected to receive evaluation in recent future. LESSONS: Course of Coronavirus Disease 19 is relatively longer, and failure rate of simple early extubation seemes higher. To reduce the likelihood of reintubation and iatrogenic injury, individualized assessment is recommended.