BACKGROUND AND OBJECTIVES Ketamine has been used in pediatric flexible fiberoptic bronchoscopy (FFB). Its efficacy and safety for sedation of adults undergoing FFB has not been thoroughly investigated, and, consequently, it is not used by most interventional bronchoscopists. We aimed to evaluate the safety and efficacy of sedation for FFB under ketamine-propofol-midazolam (KPM) compared with the fentanyl-propofol-midazolam (FPM) regimen. MATERIALS AND METHODS This was a prospective randomized trial of adult patients (n=80) undergoing FFB, randomized to receive sedation with either KPM (n=39) or FPM (n=41). Vital signs including transcutaneous carbon dioxide tension (TcPCO2) were continuously monitored. Sedation-related complications and interventions to maintain respiratory and hemodynamic stability were compared. Both operator and patient were blinded to the sedation regimen used. The operator's and patient's satisfaction from sedation were assessed following recovery. RESULTS Maximal intraprocedural TcPCO2 values and minimal oxygen saturation did not differ significantly between the KPM and FPM groups (63.2±11.4 mm Hg vs. 61.1±7.2 mm Hg) and (77.1%±12.5% vs. 81.8%±12.0%), respectively. No significant differences were noted between the KPM and FPM groups with respect to sedation-related respiratory or hemodynamic complications. The operator's and patient's satisfaction from sedation was similar between the groups. CONCLUSIONS Ketamine is as safe and effective as fentanyl for adult analgesia and sedation during FFB. In light of this observation and the fact that ketamine does not cause hemodynamic suppression, like most sedative agents, and is a potent bronchodilator, should encourage its more widespread use for adult sedation during FFB.