Quantify the outcomes following pneumothorax aspiration and influence upon chest drain insertion. This was a retrospective cohort study of patients who underwent aspiration for the treatment of a pneumothorax following a CT percutaneous transthoracic lung biopsy (CT-PTLB) from January 1, 2010 to October 1, 2020 at a tertiary center. Patient, lesion and procedural factors associated with chest drain insertion were assessed with univariate and multivariate analyses. A total of 102 patients underwent aspiration for a pneumothorax following CT-PTLB. Overall, 81 patients (79.4%) had a successful pneumothorax aspiration and were discharged home on the same day. In 21 patients (20.6%), the pneumothorax continued to increase post-aspiration and required chest drain insertion with hospital admission. Significant risk factors requiring chest drain insertion included upper/middle lobe biopsy location [odds ratio (OR) 6.46; 95% CI 1.77-23.65, p = 0.003], supine biopsy position (OR 7.06; 95% CI 2.24-22.21, p < 0.001), emphysema (OR 3.13; 95% CI 1.10-8.87, p = 0.028), greater needle depth ≥2 cm (OR 4.00; 95% CI 1.44-11.07, p = 0.005) and a larger pneumothorax (axial depth ≥3 cm) (OR 16.00; 95% CI 4.76-53.83, p < 0.001). On multivariate analysis, larger pneumothorax size and supine position during biopsy remained significant for chest drain insertion. Aspiration of a larger pneumothorax (radial depths ≥3 cm and ≥4 cm) had a 50% rate of success. Aspiration of a smaller pneumothorax (radial depth 2-3 cm and <2 cm) had an 82.6% and 100% rate of success, respectively. Aspiration of pneumothorax after CT-PTLB can help reduce chest drain insertion in approximately 50% of patients with larger pneumothoraces and even more so with smaller pneumothoraces (>80%). Aspiration of pneumothoraces up to 3 cm was often associated with avoiding chest drain insertion and allowing for earlier discharge.