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The purpose of this study was to investigate the impact of lesion proximity to the diaphragm on computed tomography (CT)-guided percutaneous biopsy yield and pneumothorax rates.An Institutional Review Board–approved retrospective review of all CT-guided percutaneous core lung biopsies at a single institution performed between August 1, 2011 and July 31, 2013 yielded 168 patients who underwent a total of 174 lung biopsies. The shortest distance of the target lesion from the diaphragm was measured on preprocedure sagittal reformatted CT images. Pathology and 2-hour postprocedure chest radiograph results were then collected from these patients.The average distance of the target lesion from the diaphragm was 8.3 cm, and biopsies resulted in nondiagnostic pathology in 27 (16%) cases. Proximity to the diaphragm was a significant predictor of nondiagnostic biopsy, with the odds of a successful biopsy increased by 67% for every 5 cm the target lesion is farther from the diaphragm (P=0.026). Distance from the diaphragm was not a significant predictor of postbiopsy pneumothorax or need for chest tube placement. These relationships hold true after adjusting for patient demographic parameters, presence of emphysema, operator level of experience, distance of the lesion from the pleural surface, target lesion size, and cavitary nature.The odds of nondiagnostic biopsy increase for lesions closer to the diaphragm; however, the odds of pneumothorax are not significantly different.