Background: Grading system for resected invasive pulmonary adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) was validated as a strong prognostic indicator. Nonetheless, the efficacy of utilizing such grading system in prognostic assessment of patients receiving neoadjuvant therapy still needs elucidating. Methods: A retrospective study was conducted including patients with resected adenocarcinoma following neoadjuvant chemotherapy or targeted therapy from August 2012 to December 2020 in Shanghai Pulmonary Hospital. All the surgical specimens were re-evaluated and graded. The prognostic value of the grading system was further validated. Results: Ultimately, a total of 198 patients were enrolled in this study, and subdivided into three cohorts according to the grading system. There were 13 (6.6%), 37 (18.7%), and 148 (74.7%) patients belonging to Grades 1, 2, and 3, respectively. IASLC grading system demonstrated significant power in prognosis differentiation of the entire cohort recurrence-free survival (RFS), p < 0.001; overall survival (OS), p < 0.001 and the neoadjuvant chemotherapy and targeted therapy cohorts separately, and was further verified as a significant prognostic indicator for RFS and OS in multivariable Cox analysis. Since the majority of the patients (84.8%) did not achieve major pathologic response (MPR), representing a wide spectrum of survival, the prognostic value of grading system in non-MPR cohort was further evaluated. Similar results were also obtained that IASLC grading system was assessed significant in univariable analysis of RFS (p < 0.001) and univariable analysis of OS (p = 0.001). Conclusions: The prognostic efficacy of pathological evaluation of the residual proportion of pulmonary adenocarcinoma post-neoadjuvant therapy using IASLC grading system was preliminarily verified. Such grading system might assist prognostic evaluation of neoadjuvant cohort other than traditional pathological parameters.