PurposeTo compare the effectiveness of 2 track sealing techniques following computed tomography (CT)–guided lung biopsy using either gelatin sponge slurry (GSS) or saline to reduce the rate of postbiopsy pneumothorax. Materials and MethodsIn this prospective study, a total of 266 patients (median age, 66.2 years; range, 25.5-89.2 years; 150 men) were included between July 2019 and January 2023. The patients referred for a CT-guided lung biopsy, in whom the needle would pass through aerated lung, were randomly assigned to either the GSS sealing technique group (n = 132) or the saline track sealing technique (n = 134) in a 1:1 ratio. All biopsies were performed using a 19-gauge coaxial needle in a tertiary hospital by 1 of 4 interventional radiologists with varying levels of experience. The outcomes were pneumothorax occurrence, pneumothorax-related intervention (simple aspiration and/or drainage), and biopsy-related hospital stay length. ResultsPneumothorax rates were 12.1% in the GSS group and 24.6% in the saline group (P = .008). Hospital length of stay was significantly shorter in the GSS group (P = .003). There was no significant difference in pneumothorax-related intervention between the groups (6.8% vs 12.7%; P = .107). In the multiple logistic regression analysis, track sealing with GSS was a protective factor for pneumothorax (odds ratio [OR], 0.44; 95% CI, 0.22–0.87; P = .019), and emphysema was associated with higher risk of pneumothorax (OR, 2.67; 95% CI, 1.31–5.44; P = .007). ConclusionsTrack sealing with GSS following a CT-guided lung biopsy is significantly more efficient than saline in reducing postbiopsy pneumothorax and results in shorter hospital stay.