BACKGROUND: Adjuvant chemotherapy demonstrated a clear benefit in resected non-small cell lung cancer (NSCLC) with nodal disease (stages II-III), and a minimal benefit in tumors >4 cm (stage II, TNM 8th edition). Pleural invasion (PL), classified as visceral pleural invasion (VPI, which includes PL1 and PL2, and parietal pleural invasion (PL3), is an established negative prognostic factor. However, whether PL should influence the decisional algorithm of postoperative chemotherapy is controversial. METHODS: A survival analysis of NSCLC patients who underwent radical surgery between 2010 and 2015 included in the SEER database was performed. Tumor stage and size, number of examined and positive nodes, histology, PL, and treatment data were extracted. Propensity score matching was performed. The benefit of chemotherapy was analyzed in two subgroups: standard of care (SOC), including patients with positive nodes or tumors ≥ 4 cm; non-SOC, including patients with tumors < 4 cm and negative nodes. RESULTS: Records of 30,858 patients were extracted. 11,708 patients were included in the propensity score-matched analysis. In the SOC subgroup, including 8089 patients, all pleural invasion degrees were associated with progressively increased risk for death and shorter overall survival (OS), independently from chemotherapy administration. However, chemotherapy significantly improved the median OS regardless of the extent of PL. In the non-SOC subgroup, including 3619 patients, only PL3 was associated with increased mortality. The administration of chemotherapy did not improve survival outcomes. CONCLUSION: Chemotherapy should be strongly recommended in patients in the SOC-subgroup with pleural invasion. VPI is not associated with unfavorable prognosis in the non-SOC subgroup.