Purpose: Histological verification of pulmonary lesions is important to ensure correct treatment. Computed tomographic (CT) transthoracic core biopsy is a well-established procedure for this. Comparison of available studies is difficult though, as technical and patient characteristics vary. Using a standardized biopsy technique, we evaluated our results for CT-guided coaxial core biopsy in a semi-automatic technique. Materials and Methods: Within 2 years, 664 consecutive transpulmonary biopsies were analyzed retrospectively. All interventions were performed using a 17/18G semi-automatic core biopsy system (4 to 8 specimens). The incidence of complications and technical and patient-dependent risk factors were evaluated. Results: Comparing the histology with the final diagnosis, the sensitivity was 96.3?%, and the specificity was 100?%. 24 procedures were not diagnostic. In all others immunohistological staining was possible. The main complication was pneumothorax (PT, 21.7?%), with chest tube insertion in 6?% of the procedures (n?=?40). Bleeding without therapeutic consequences was seen in 43 patients. There was no patient mortality. The rate of PT with chest tube insertion was 9.6?% in emphysema patients and 2.8?% without emphysema (p?=?0.001). Smokers with emphysema had a 5 times higher risk of developing PT (p?=?0.001). Correlation of tumor size or biopsy angle and the risk of PT was not significant. The risk of developing a PT was associated with an increasing intrapulmonary depth of the lesion (p?=?0.001). Conclusion: CT-guided, semiautomatic coaxial core biopsy of the lung is a safe diagnostic procedure. The rate of major complications is low, and the sensitivity and specificity of the procedure are high. Smokers with emphysema are at a significantly higher risk of developing pneumothorax and should be monitored accordingly. Key points: ??Using an 18G core biopsy system with 6 specimens will allow immunohistological staining with high sensitivity and specificity. ??Smokers with emphysema are at a significantly higher risk of developing a pneumothorax. Citation Format: ??Schulze R, Seebacher G, Enderes B. et?al. Complications in CT-Guided, Semi-Automatic Coaxial Core Biopsy of Potentially Malignant Pulmonary Lesions. Fortschr R?ntgenstr 2015; 187: 697???702