Abstract: Objective To compare acute inflammatory responses and immunosuppression to lobectomy in lung cancer patients with video-assisted thoracoscopic surgery (VATS) and posterolateral thoracotomy (PLT). Methods A total of 103 patients who underwent either a VATS (n=51) or a PLT (n=52) lobectomy for early non-small cell lung cancers (NSCLC, stage Ⅰ) were recruited for this study. Blood samples of the participants were taken pre-operatively and at 24 h and 72 h post-operatively for analyses of C-reactive protein (CRP), interleukin (IL)-6, IL-2 receptors (IL-2R), and serum amyloid A (SAA). Blood samples taken pre-operatively and at 2 d and 7 d post operations were also analyzed for total lymphocytes, NK cells, CD4⁺T, and CD8⁺T. Results Patients in the VATS group lost significantly less blood than those in the PLT group (P=0.001). Patients in the PLT group had significantly higher serum SAA than those in the VATS group (P=0.006). Significant reduction of CD8⁺T was found in the patients with PLT after operations (P<0.01). Patients in the PLT group had significantly lower at CD8⁺T 7 d post operations than those in the VATS group (P=0.015). Conclusion VATS pulmonary lobectomy is associated with reduced acute inflammatory responses and immunosuppression compared with the PLT approach.