Background Percutaneous CT-guided lung core-needle biopsy is a frequently performed and generally safe procedure. However, with advances in the management of lung cancer, there is a need for a greater amount of tissue for tumor genomic profiling and characterization. Purpose To determine whether the number of core samples obtained with percutaneous CT-guided lung biopsy is associated with postprocedural complications. Materials and Methods This retrospective study included consecutive patients who underwent percutaneous CT-guided coaxial lung core-needle biopsy for suspected primary lung cancer between November 2012 and August 2023 at an academic tertiary referral hospital. Patient data from medical records were collected, including demographics, lesion size and distance from pleura, and number of obtained biopsy samples. Postprocedural complications of pneumothorax, chest tube placement, perilesional hemorrhage, and hemoptysis were recorded. Multivariable logistic regression models were used to assess whether the number of cores was a predictive factor for lung biopsy complications. Results A total of 827 patients (mean age, 70.9 years ± 9.6 [SD]; 474 [57.3%] female patients) were included. The median lesion size was 22 mm (IQR, 15-34 mm), with 517 of 827 (62.5%) patients diagnosed with lung adenocarcinoma. Pneumothorax was noted in 171 of 827 (20.7%) patients, with a chest tube placed in 32 of 827 (3.9%), perilesional hemorrhage in 353 of 827 (42.7%), and hemoptysis in 20 of 827 (2.4%) patients. The median number of samples obtained was four (range, one to 12). Multivariable analysis showed no evidence of an association between the number of core samples obtained and any complications: pneumothorax (coefficient, -0.02; P = .81), chest tube (coefficient, 0.18; P = .26), perilesional hemorrhage (coefficient, -0.03; P = .63), or hemoptysis (coefficient, -0.10; P = .60). Conclusion In patients suspected of having lung cancer who underwent percutaneous CT-guided coaxial lung core biopsy, there was no evidence of an association between the number of core biopsy samples obtained and any postprocedural complications. © RSNA, 2024 See also the editorial by Zuckerman in this issue.