Background: Sedation combined with local anesthesia during bronchoscopy is widely accepted in America and Europe, and receiving great attention in China. This study aimed to investigate the safety and efficacy of fentanyl combined with midazolam for bispectral index (BIS) titrated conscious sedation during bronchoscopy in the Chinese population. Methods: Data from 436 patients who underwent bronchoscopy under local anesthesia (LA group) or BIS-guided conscious sedation combined with local anesthesia (FM group) were retrospectively analyzed. The analysis included vital signs, adverse events recorded during the procedure, and questionnaire information, such as patient tolerance and satisfaction, operator satisfaction, and the cough score noted after the procedure. Results: A total of 225 patients in the LA group, and 211 in the FM group were enrolled in the study. The blood pressure and oxygen saturation were significantly higher in the LA group than in the FM group during bronchoscopy (P<0.001). The heart rate was significantly faster in the LA group at T3max, T3min and T4 than in the FM group. The incidence of hypoxia and bradycardia was higher in the FM group than in the LA group, whereas incidence of hypertension and tachycardia was lower. Patient satisfaction and tolerance of the procedure were significantly better in the FM group. visual analog scale (VAS) scores for cough and operator satisfaction were better in the FM group than in the LA group. Sub-group analysis (inspection, biopsy and transbronchial biopsy guided by radial endobronchial ultrasound (rEBUS-TBB)) indicated that the vital signs, adverse event(hypoxia) and patient satisfaction of the two groups were similar to the previous results. However, the VAS scores for operators’ satisfaction was no significant difference between the two groups in patients undergoing inspection. Conclusions: The conscious sedation regimen of fentanyl combined with midazolam monitored by BIS during bronchoscopy is safe and effective. Although the incidence of hypoxia and bradycardia was higher, the patient’s tolerance and physician’s satisfaction were significantly improved, especially during lengthy procedures, such as intrabronchial biopsy and transbronchial biopsy guided by radial endobronchial ultrasound. Trial registration: The study was approved by the ethics committee of Changzhou first people's Hospital (2019-020).