Background: Advances in bronchoscopy have impacted the practice patterns in the sampling of thoracic lymph nodes and lung lesions. Objectives: The aim of the study was to study the trends in utilization of mediastinoscopy, transthoracic needle aspiration (TTNA), and bronchoscopic transbronchial sampling. Methods: We conducted an analysis of patient claims for sampling of thoracic lymph nodes and lung lesions in the Medicare population and a sample of the commercial population between 2016 and 2020. We used Current Procedural Terminology codes to identify mediastinoscopy, TTNA, and bronchoscopic transbronchial sampling. Post-procedural pneumothorax rates were assessed by procedure type including subset analyses for patients with chronic obstructive pulmonary disease (COPD). Results: Between 2016 and 2020, utilization of mediastinoscopy has decreased in both the Medicare and commercial populations (−47.3% and −65.4%, respectively), while linear endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) has increased only in the Medicare population (+28.2%). Percutaneous lung biopsy claims dropped by −17.0% in the Medicare and −41.22% in the commercial population. The use of bronchoscopic TBNA and forceps biopsy declined in both populations, but the reliance on a combination of guided technology (radial EBUS-guided and navigation) grew in the Medicare and commercial populations (+76.3% and +25%). Rates of post-procedural pneumothorax were significantly higher following percutaneous biopsy compared to bronchoscopic transbronchial biopsy. Conclusions: Linear EBUS-guided sampling has surpassed mediastinoscopy as the technique for sampling thoracic lymph nodes. Transbronchial lung sampling is increasingly being performed with guidance technology. This trend is aligned with favorable rates of post-procedure pneumothorax for transbronchial biopsy.