Background: Transthoracic needle biopsy (TNB) is one of the routine procedures for thoracic diseases, especially nodules or consolidation. The procedure can be guided by imaging tools, such as computed tomography (CT) scan and ultrasonography (US). This study reports the results of a five-year experience of transthoracic imaging-guided needle biopsy in a respiratory referral hospital. Methods: We searched for a monthly sampling database in the procedure room from 2020 to 2024 and identified all transthoracic imaging-guided needle biopsies, either by CT or US-guided. We excluded a few data samples if there was a repetition of the data register. Data regarding pathology and procedure-related complications were analyzed, with the primary outcomes being disease proportion and positivity rate of the procedure. Results: A total of 1,591 procedures were included in our final analysis. Almost all procedures (99.6%) used a 16-gauge needle core biopsy size. Computed tomography was used predominantly (89.9%) to guide the procedure rather than ultrasound. Adenocarcinoma was the most frequent pathology result of TNB (37.7%). The complications were rare (1.6%) and there was zero mortality reported within 24 hours after TNB procedures. Lung cancer was the most reported case, followed by lymphoma and tuberculosis (TB). The overall accuracy of the TNB procedure in lung and mediastinal consolidation was 96.3%. Conclusions: Transthoracic needle biopsy has high accuracy and is considered a safe procedure with minor complications. © Mattioli 1885.