Assessment of the efficacy and complications associated with performing bronchoscopy-guided percutaneous tracheostomy in COVID-19 and non–COVID-19 patients. Prospective observational study conducted between March of 2020 and February of 2022. All adult patients who underwent elective bronchoscopy-guided percutaneous tracheostomy were included. The efficacy of the procedure was evaluated based either on the success rate in the execution or on the need for conversion to open technique. Percutaneous tracheostomy-related complications were registered during the procedure. We performed 6-month follow-up for identifying late complications. During the study period, 312 bronchoscopy-guided percutaneous tracheostomies were analyzed. One hundred and eighty-three were performed in COVID-19 patients and 129 among non–COVID-19 patients. Overall, 64.1% (200) of patients were male, with a median age of 66 (interquartile range 54–74), and 65% (205) presented at least 1 comorbidity. Overall, oxygen desaturation was the main complication observed (20.8% 65), being more frequent in the COVID-19 group occurring in 27.3% (50) with a statistically significant difference versus the non–COVID-19 patients’ group (11.6% 15); P < .01). Major complications such as hypotension, arrhythmias, and pneumothorax were more frequently observed among COVID-19 patients as well but with no significant differences. Percutaneous tracheostomy could be executed quickly and satisfactorily in all the patients with no need for conversion to the open technique. Likewise, no suspension of the procedure was required in any case. During 6-month follow-up, we found an incidence of 0.96% (n = 3) late complications, 2 tracheal granulomas, and 1 ostomal infection. Bronchoscopy-guided percutaneous tracheostomy can be considered an effective and safe procedure in COVID-19 patients. Nevertheless, it is highly remarkable that in the series under study, a great number of COVID-19 patients presented oxygen desaturation during the procedure.