Objective To investigate the incidence of difficult intubation with double‑lumen endobronchial tube (DLT) in anesthesia induction, and discuss how to deal with difficult intubation with DLT and strategy to achieve pulmonary isolation during surgery. Methods Medical records from patients scheduled for intubation with DLT in the Anesthesia Information Database of Shanghai Chest Hospital from May 2009 to May 2012 were retrospectively analyzed to search cases using the following three keywords: "difficult intubation", "intubation with DLT" and "one‑lung ventilation (OLV)". The primary outcome was the incidence of difficult intubation with DLT, while the secondary outcomes were airway evaluation in patients with difficult intubation before surgery, management strategy to solve difficult intubation, the way to achieve perioperative lung collapse, and perioperative complications related to intubation. Results A total of 11 017 patients were included in the current study. Difficult intubation happened in 112 patients (1.0%). Among the 112 patients, 22 patients (19.6%) had predictable or suspected difficult airway, while the other 90 patients (80.4%) showed no obvious clinical signs of difficult intubation before induction. Furthermore, 90 patients (80.4%) adopted two or more types of intubation devices. There were 22 patients who were intubated with single‑lumen endotracheal tubes after induction, where 2 patients were successfully implanted with DLT through the guidance of exchange catheters for pulmonary isolation, 13 patients were implanted with bronchial blockers under a fiberbronchoscope, and 7 patients received low tidal volume ventilation. There was no case of severe cardiovascular complications. Conclusions DLT has strict requirements for the conditions of glottic exposure, and airway assessment before anesthesia should be more cautious. The use of visual tools improves the safety and effectiveness of intubation with DLT. Bronchial blockers provide more choices for difficult intubation with DLT.