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Background: Computed tomography (CT)-guided transthoracic needle biopsy (TNB) could damage lung structures and may disseminate tumor cells into the airway, blood vessels, and pleural cavity, affecting post-operative outcomes. Several studies have investigated the effects of TNB on the prognosis of patients, but the effects remain unclear. This study aimed to investigate whether TNB increases the risk of recurrence of resected stage IA non-small cell lung cancer (NSCLC)., Methods: In this retrospective study, we enrolled 1,077 patients with stage IA NSCLC who underwent curative resection from 2010 to 2020. Recurrence risk factors were evaluated using Cox regression analyses. A multiple logistic regression model, including age, sex, smoking history, total tumor size, invasive tumor size, histology, histologic differentiation, lymphatic invasion, vascular invasion, perineural invasion, and the number of harvested lymph nodes (LNs), was used to calculate the propensity score., Results: According to the pre-operative TNB, patients were classified into the no-TNB (n=823) and TNB (n=190) groups. After propensity score matching analysis, 380 patients were included in the no-TNB group (1:2 matching). Multivariable Cox analysis revealed that pre-operative TNB was a negative prognostic factor in patients with surgically resected stage IA NSCLC [hazard ratio (HR), 3.15; 95% confidence interval (CI): 1.49-6.67; P=0.003]. The 5-year locoregional and overall recurrence-free survival (RFS) rates were significantly lower in the TNB group than in the no-TNB group (88.3% vs . 96.8%, P=0.001; and 84.2% vs . 93.7%, P=0.02, respectively)., Conclusions: For patients with stage IA NSCLC, pre-operative TNB was a negative prognostic factor for recurrence. Surgical diagnosis and treatment without pre-operative tissue diagnosis may be considered first in patients with clinically early lung cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-419/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)