Purpose To assess the effect of extrapleural autologous blood injection (EPABI) technique on pneumothorax development before and after coaxial needle withdrawal (CNW) and intervention rate for pneumothorax. To analyze the risk factors of pneumothorax and parenchymal hemorrhage. Materials and Methods The records of 288 patients who had lung biopsies were analyzed. Of these patients, 188 received EPABI (group-A) before penetrating the parietal pleura, and the remaining did not (group-B). Intraparenchymal autologous blood patch injection was applied at the end of the procedure. The pneumothorax rates before/after CNW and intervention requirement for pneumothorax were compared between groups. The risk factors of pneumothorax before/after CNW and parenchymal hemorrhage were assessed with stepwise logistic regression. Results The pneumothorax rate before CNW was significantly lower in group-A (5.92%) than in group-B (19.10%) (p = 0.029). Pneumothorax risk before CNW was reduced if EPABI was applied and skin-to-pleura distance increased. The pneumothorax rate after CNW was similar between two groups (group-A: 6.94%, group-B: 8%), while emphysema grade along the needle path and procedure duration was the significant risk factor. The intervention requirement for pneumothorax was significantly lower in group-A (6.38%) than in group-B (16%) (p = 0.012). Needle aspiration requirement was significantly reduced in group-A. The rate of external drainage catheter and chest tube placement was similar in both groups. The risk factors of parenchymal hemorrhage were overall emphysema grade of the lung, target-to-pleura distance, and target size. Conclusion Use of EPABI along with IAPBI significantly decreased the pneumothorax rate during biopsy procedure and the intervention rate compared to IAPBI-alone.