The case series illustrates clinical challenges associated with performing fiberoptic bronchoscopy (FOB) on patients with severe respiratory and cardiovascular diseases. Standard respiratory support methods may be insufficient or may pose risks in this population. The first case involved a patient with a congenital heart defect, unstable hemodynamics, and suspected inflammatory changes in the lungs who required diagnostic FOB due to bleeding from the respiratory tract. Use of high-flow nasal oxygen therapy (HFNOT) allowed for safe performance of FOB, minimizing the risk of barotrauma-related complications. The second patient was diagnosed with Melnick-Needles syndrome, chronic respiratory failure and bronchial cartilage chondromalacia, which can be responsible for complications during standard FOB. HFNOT was also used during the procedure, which prevented complications resulting from anatomical limitations and barotrauma. These cases suggest that HFNOT is an effective alternative to traditional respiratory support methods during FOB for patients at a high risk of complications, especially those with congenital heart defector airway anomalies.