Purpose Patient characteristics associated with difficult tracheal intubation using a flexible bronchoscope (FB) under general anesthesia have not been prospectively evaluated. This observational study aimed to identify demographic and morphologic factors associated with difficult FB intubation. Methods We recruited 420 adult elective surgery patients undergoing tracheal intubation during general anesthesia. Patients characteristics were recorded including age, sex, weight, height, body mass index, American Society of Anesthesiologists physical status, history of snoring, obstructive sleep apnea, Mallampati score, upper lip bite test score, neck circumference and skinfold thickness, maximal neck flexion and extension angles, absence of teeth, Cormack and Lehane grade, presence of blood or secretions during intubation, as well as the inter-incisor, thyromental, sternothyroid, and manubriomental distances. The time (duration) needed to complete intubation (primary endpoint) and the number of attempts needed were correlated with these patient characteristics in a multivariable analysis. Results Intubation was successful on the first attempt in 409/420 patients (97%). Seven patients (1.7%) needed more than one attempt. Failure to intubate with the FB occurred in four patients (1%). A correlation was found between intubation duration and visibility impaired by secretions or blood (P \ 0.001), higher neck skinfold thickness (P \ 0.001), and larger endotracheal tube diameter (relative to a constant 5.5 mm FB; P \ 0.001). Conclusions The presence of secretions or blood that impair FB glottic visualization, a larger diameter endotracheal tube on the same size FB, as well as higher neck skinfold thickness may prolong the duration of FB intubation under general anesthesia. Trial registration www.clinicaltrials.gov (NCT02769819); registered 5 May, 2016.