Single-use flexible bronchoscopes (SFBs) are increasingly used to minimize cross-infection risk, particularly in immunocompromised and intensive care unit patients. However, broader adoption requires cost analysis. We conducted a 1-year cost-minimization analysis comparing SFBs and reusable flexible bronchoscopes (RFBs) at a tertiary care university hospital. We evaluated the costs per procedure, considering capital equipment, maintenance, repair, reprocessing, and overhead costs. We also analyzed the impact of annual procedure volume on costs and performed a sensitivity analysis to assess the effect of uncertainty on costs. A total of 1394 bronchoscopies were performed. RFBs were less expensive for an annual volume of >50 bronchoscopies/year, with a 22% lower cost per procedure than that for SFBs (€203 vs. €259). This cost advantage became increasingly favorable with an increasing number of procedures, reaching a plateau after exceeding 250 bronchoscopies/year. The capital equipment, the annual number of bronchoscopies, and reprocessing were the major cost drivers for RFBs. During nonworking hours, the cost per procedure of RFBs ranged from €349.45 to €392.29. Using RFBs during interventions involving a high risk of bronchoscope damage (frequency of damage >10%) would increase the cost per bronchoscopy to >€263 (exceeding the cost of SFBs). RFBs were 22% less expensive than SFBs for services with a moderate to high volume of bronchoscopies. However, this difference could not justify using RFBs in patients with a high cross-infection risk. SFBs might be less costly for procedures outside working hours and interventions involving a high risk of bronchoscope damage.