Introduction: Sedation during flexible bronchoscopy can be administered by a second physician, an anesthesiologist or as nurse-administered sedation (NAS). Propofol is often administered by non-anesthesiologists. It is unclear whether complications differ with various sedation protocols. Methods: We searched PubMed for clinical trials of sedation during bronchoscopy and conducted a systematic review of complications (death ≤24 h post-procedure or intensive care unit (ICU) admission/predefined cardiopulmonary escalation [CPE]). Outcomes were analyzed according to the staff administering sedation, complexity of procedure, for propofol-containing regimes, and the ASA physical status classification of the patient. Results: This analysis (120 articles, 39,475 procedures) showed a mortality rate of 0.01% for sedation bronchoscopy. ICU admission rate was 0.12%, and CPE was reported in 0.57%. Significantly higher CPE was recorded for anesthesiologists compared to NAS and second physicians (1.16% vs. 0.65% vs. 0.07%, respectively, p < 0.001) with higher ICU admission for NAS compared to anesthesiologists and second physicians (0.35% vs. 0.00% vs. 0.03%, respectively, p < 0.001). Endobronchial ultrasound did not increase complication rates. Admission to ICU and CPE remained <1% in propofol-containing regimes, although complications were slightly lower without propofol. Comparison of lower risk ASA 1–2 studies compared to studies with ASA 1–3 showed no significant difference in outcome. Conclusion: Sedation bronchoscopy is a safe procedure. The staff administering sedation may react differently to periprocedural respiratory and cardiovascular events. Propofol application is not associated with a clinically relevant increase in complication rate. There is no evidence that ASA status is a predictor of individual risk at bronchoscopy.