Background <p>Cryobiopsy is used in addition to conventional sampling during endobronchial ultrasound (rEBUS)-guided bronchoscopy for peripheral pulmonary lesions (PPLs) to improve diagnostic yield. However, the incremental risk of procedure-related pulmonary infection remains poorly quantified in routine clinical practice.</p> Methods <p>We retrospectively analyzed consecutive patients who underwent rEBUS-guided bronchoscopy for PPLs between January 2019 and March 2022. Patients were categorized into those undergoing combined conventional biopsy and cryobiopsy and those undergoing conventional biopsy alone. Pulmonary infectious complications occurring within 4 weeks after bronchoscopy were assessed. Propensity score matching was performed to adjust for baseline differences and to evaluate the impact of cryobiopsy on pulmonary infectious complications. Sensitivity analyses using overlap weighting were also conducted.</p> Results <p>After propensity score matching, 756 patients were included in the matched cohort (combined cryobiopsy group: <i>n</i> = 252; conventional biopsy group: <i>n</i> = 504). Pulmonary infectious complications occurred more frequently in the combined cryobiopsy group than in the conventional biopsy group (4.8% vs. 1.8%). Adding cryobiopsy was associated with an increased risk of pulmonary infectious complications (odds ratio, 2.84; 95% confidence interval, 1.15–6.99; <i>P</i> = 0.023), corresponding to an absolute risk increase of 3.0% and a number needed to harm of 33. These findings were consistent in sensitivity analyses using overlap weighting.</p> Conclusions <p>Adding cryobiopsy to conventional sampling in rEBUS-guided bronchoscopy is associated with a higher risk of pulmonary infectious complications. These findings provide quantitative evidence to guide patient selection and procedural planning.</p>