Complete pathologic response (CPR) is an acceptable surrogate for survival in clinical trials but it occurs infrequently in patients with NSCLC receiving neoadjuvant chemotherapy (NCT). Therefore, we studied the impact of major pathologic response (MPR) for predicting survival of patients with NSCLC receiving NCT. We also tested a newly reported scoring system-the prognostic score (PRSC)-which combines T category, lymph node status, and MPR status. We analyzed CPR and MPR, defined as 0% and less than or equal to 10% viable tumor cells, respectively, in 339 patients with NSCLC with various histologic types who had been treated with NCT followed by complete surgical resection. We evaluated the relationships between CPR, MPR, or PRSC and overall survival using the Kaplan-Meier method and Cox regression multivariate models, accounting for known prognostic factors, such as age, gender, histologic subtype, and pathologic stage. Among all 339 patients, the Kaplan-Meier method revealed that patients with CPR and MPR had better survival. MPR identified a favorable group of patients who experienced survival similar to patients with CPR. Nevertheless, patients with no MPR had a significantly reduced probability of survival. Furthermore, univariate and multivariate Cox proportional hazards regression analysis revealed that MPR and PRSC were significantly associated with overall survival. Our data suggest that MPR can be used as an end point for overall survival in different histologic types for evaluation of therapeutic agents in clinical trials exploring NCT. We also confirmed that PRSC had a prognostic impact, differentiating patients into three prognostic groups, but not superior compared with MPR alone or the TNM8 systems.