Background Ideal sedation and analgesia strategies for fiberoptic bronchoscopy have not been found. At present, propofol based sedation strategy still has some defects, such as respiratory depression and blood pressure drop, which is difficult to meet the requirements of safety and effectiveness at the same time. The aim of this study was to compare the clinical efficacy of propofol/remifentanil with propofol/esketamine for patient sedation during fiberoptic bronchoscopy. Method: Patients undergoing fiberoptic bronchoscopy were randomly assigned to receive either propofol/ remifentanil (PR group; n = 42) or propofol/esketamine (PK group; n = 42) for sedation and analgesia. Changes in blood pressure, heart rate, and oxygen saturation were monitored. The incidence of adverse reactions, the total amount of propofol usage were recorded. satisfaction level of patients and bronchoscopists was evaluated. Results After sedation, the arterial pressure and heart rate of patients in the PK group were stable without significant decrease. Decreases in diastolic blood pressure, mean arterial pressure, and heart rate were observed in patients in the PR group (P < 0.05). The dosage of propofol in the PR group was significantly higher than that in the PK group (144.43 ± 38.19 mg vs. 124.98 ± 35.30 mg, P = 0.012). Patients in the PR group showed more intraoperative cough (28 vs. 7, P < 0.01), postoperative vomiting (22 vs. 13, P = 0.076) and vertigo (15 vs. 13, P = 0.003). Bronchoscopists in the PK group showed more satisfaction. Conclusion Compared with remifentanil, the combination of esketamine with propofol in fiberoptic bronchoscopy provided more stable intraoperative hemodynamics, lower dosage of propofol, fewer incidence of adverse events, and greater bronchoscopists satisfaction.