The aim of this study was to evaluate the risk of pneumothorax and need for chest tube insertion in CT-guided lung biopsies and identify predictors focusing on pulmonary emphysema determined with quantitative computed tomography. To that end, we retrospectively analysed the incidence of pneumothorax and chest tube insertion in 371 CT-guided lung biopsies with respect to the quantitative emphysema score determined with the density mask technique. Other possible impact factors considered were lesion diameter, length of biopsy pathway within the lung parenchyma, lung lobe, needle size, puncture technique, patient positioning and interventionalist’s level of experience. Quantitative emphysema scores of the lung were significantly higher in patients who developed instant pneumothorax (27%, p < 0.0001), overall pneumothorax (38%, p = 0.001) and had chest tube insertion (9%, p = 0.006) compared to those who did not when analysed with the Mann–Whitney U-test. In logistic regression analysis with inclusion of the other possible impact factors, the quantitative emphysema score remained a statistically significant predictor for all three output parameters. This was confirmed with least absolute shrinkage and selection operator (Lasso) regression analysis. In conclusion, quantitatively determined pulmonary emphysema is a positive predictor of the pneumothorax rate in CT-guided lung biopsy and likelihood of chest tube insertion.