Purpose <p>To evaluate the effectiveness of wound negative-pressure–assisted (NPA) localization in facilitating pulmonary expansion during intraoperative cone-beam computed tomography (CBCT) localization for thoracoscopic resection of small pulmonary nodules.</p> Methods <p>A retrospective comparative study included 55 consecutive patients who underwent wedge resection for small lung tumors using uniportal video-assisted thoracoscopic surgery (VATS) with CBCT localization between June 2022 and December 2024. Patients were grouped by localization technique: Group 1 received NPA and Group 2 did not. Primary outcomes were CBCT localization workflow time and CBCT-defined incomplete lung expansion/residual pleural air (CTILA) occurrence. Univariate comparisons used Welch’s t-test for continuous variables and chi-square tests for categorical variables. Multivariable logistic regression assessed factors associated with CTILA, and multivariable linear regression analyzed CBCT localization workflow time.</p> Results <p>Baseline demographic and clinical characteristics were similar between groups. CBCT localization workflow time was significantly shorter in Group 1 than in Group 2 (17.31 ± 7.13 vs. 25.69 ± 9.57 min; mean difference − 8.38 min; 95% CI − 13.00 to − 3.76; p = 0.0007; Hedges’ g = − 0.987). CTILA occurred less frequently in Group 1 (3/29, 10.3%) than in Group 2 (13/26, 50.0%) (risk difference − 39.7%, 95% CI − 61.8% to − 17.5%; Fisher’s exact p = 0.0023; odds ratio 8.67). In a multivariable model adjusted for airway management type, smoking exposure, and nodule depth, the non-NPA group remained associated with a higher likelihood of CBCT-defined incomplete lung expansion/residual pleural air (adjusted OR 7.56, 95% CI 1.03–55.61; p = 0.047).</p> Conclusion <p>NPA localization was associated with shorter CBCT localization workflow time and a lower rate of CTILA during intraoperative CBCT localization for thoracoscopic resection of small pulmonary nodules.</p> Graphical abstract <p></p>