Background: Video-assisted thoracic surgery (VATS) is currently established as the preferred approach for surgical resection of early-stage lung cancer and has been recommended by multiple clinical associations. This study aimed at evaluating the cost-effectiveness of powered vs manual staplers in video-assisted thoracic surgery (VATS) for lung lobectomy in support of hospital-based health technology assessment.Methods: Clinical and economic comparisons between powered endoscopic staplers (PES) and manual endoscopic staplers (MES) in VATS lobectomies were conducted using a decision tree model from the perspective of hospital administrators. Prolonged air leak (PAL) was selected as the surgery complication for the model. Clinical performances measured by PAL rates for the staplers were obtained from a targeted literature review. The economic parameters used in the model were based on results from real-world data analysis in China. The outcomes used in the cost-effectiveness analysis were total costs and post-discharge 6-month reoperation rates. Cost-effectiveness was measured by the incremental cost per reduction of reoperation. Model stability was evaluated using both one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: Deterministic calculation results showed powered staplers dominated manual stapler, with lower per-episode costs (CNY 83,487 for PES vs CNY 86,239 for MES) and lower reoperation rates (0.54% for PES vs 0.63% for MES). One-way sensitivity analysis and PSA results further supported that the powered stapler was the dominant strategy for VATS lobectomies. Conclusions:The cost-effectiveness analysis demonstrated powered staplers are cost-effective compared to manual staplers in VATS lobectomies.