Background: Response to preoperative systemic therapy may provide valuable information regarding tumor biology and prognosis. This is increasingly relevant nowadays considering the promising results from preoperative chemoimmunotherapy. This study aims to examine the prognostic role of preoperative chemosensitivity defined by TNM stage change in NSCLC. Methods: Patients with histologically confirmed clinical stage II-III NSCLC who have received preoperative chemotherapy followed by R0 curative surgery were identified in the NCDB between 2006 and 2017. Patients who have developed metastasis at the time of surgery, received any perioperative radiotherapy or single agent chemotherapy, or died within 90 days of surgery, were excluded. Preoperative chemosensitivity is categorized as ypT0N0, downstaged (pTNM < cTNM, excluding ypT0N0), and not downstaged (pTNM ≥ cTNM). Logistic regression was used to evaluate associations between chemosensitivity and demographic, clinical, and pathological factors. Log-rank was used for survival analysis and adjusted by cox regression for age, gender, race, year of diagnosis, academic center, insurance, comorbidity, histology, and clinical stage. Results: A total of 1266 patients were included, of whom 104 (8.2%) had ypT0N0, 575 (45.4%) were downstaged, while 587 (46.4%) were not. Female, diagnosis in recent years, treatment at academic centers, and squamous histology were significantly associated with better chemosensitivity, while clinical TNM stage, age, race, and comorbidity were not. Five-year overall survival rate is 81.2%, 57.7%, and 46.2%, respectively (log-rank p < 0.001). After Cox regression adjustment, compared with not downstaged, ypT0N0 (HR 0.28, 95% CI 0.17 – 0.45) and downstaged (HR 0.61, 95% CI 0.51 – 0.74) were independently associated with improved postoperative survival. Conclusions: Preoperative chemosensitivity defined by TNM stage change before and after chemotherapy may prognosticate NSCLC after curative surgery. It may be a useful clinical tool to identify patients with high risk of treatment failure after neoadjuvant chemoimmunotherapy in the future.