The influence of various variables on the rate of pneumothorax and intrapulmonal hemorrhage associated with computed tomography (CT)-guided transthoracic needle biopsy of the lung were evaluated retrospectively. One hundred and thirty-three patients underwent CT guided biopsy of a pulmonary lesion. Two patients were biopsied twice. Variables analyzed were lesion size, lesion location, number of pleural needle passes, lesion margin, length of intrapulmonal biopsy path and puncture time. Eighteen-gauge (18G) cutting needles (Trucut, Somatex, Teltow, Germany) were used for biopsy. Pneumothorax occurred in 23 of 135 biopsies (17%). Chest tube placement was required in three out of 23 cases of pneumothorax (2% of all biopsies). Pneumothorax rate was significantly higher when the lesions were located in the lung parenchyma compared with locations at the pleura or chest wall (P < 0.05), but all pneumothorax cases which required chest tube treatment occurred in lesions located less than 2 cm from the pleura. Longer puncture time led to an increase in pneumothorax rate (P < 0.05). Thirty-seven (27%) out of 135 biopsies showed perifocal hemorrhage. Intrapulmonal biopsy paths longer than 4 cm showed significantly higher numbers of perifocal hemorrhage and pneumothorax (P < 0.05). Significantly more hemorrhage occurred when the pleura was penetrated twice during the puncture (P < 0.05). Lesion size <4 cm is strongly correlated with higher occurrence of perifocal hemorrhage (P < 0.05). Lesion margination showed no significant effect on complication rate. CT-guided biopsy of smaller lesions correlates with a higher bleeding rate. Puncture time should be minimized to reduce pneumothorax rate. Passing the pleura twice significantly increases the risk of hemorrhage. Intrapulmonal biopsy paths longer than 4 cm showed significantly higher numbers of perifocal hemorrhage as well as pneumothorax.