Epidermal growth factor receptor (EGFR) and programmed death ligand 1 (PD-L1) are cell surface proteins that interact in the context of immune evasion to promote cancer growth. Associations between PD-L1 expression level and clinico-pathologic features of EGFR mutated (EGFR-mt) non-small cell lung cancer (NSCLC), as well as response to Osimertinib (Osi) are unclear. We retrospectively analyzed clinical outcomes in patients with EGFR-mt Stage IV NSCLC treated with first line (1 L) Osi at three New York City (NYC) hospitals between 2018-2023. Progression-free survival (PFS) and overall survival (OS) were calculated using log rank test and cox proportional hazard model. 101 patients were included for final analysis. Demographics consistent with historic data. 52 patients (51 %) had PD-L1 negative disease and 11 patients (11 %) had PD-L1 ‚â•50 %. 56 patients (62 %) had brain metastases throughout their disease course. There was an 85 % response rate (RR) overall favoring PD-L1 negative disease (92 % vs 78 %) with a significantly lower odds of response for the PD-L1 positive group (Odds ratio (OR) 0.29; 95 % CI: 0.08-0.92, p = 0.046). In a multivariate analysis controlling for TP53 mutation status, OR 0.31, 05 % CI: 0.01-1.00, p = 0.063. PFS favored PD-L1 negative patients (22.7 vs 15.4 months) with hazard ratio (HR) of 1.49, p = 0.10. OS similarly favored PD-L1 negative patients (38.8 vs 31.4 months) with HR 1.53, p = 0.12. In a multivariate analysis controlling for TP53 mutations, PD-L1 positivity was associated with a trend towards reduced response to first line treatment with Osimertinib, as well as toward higher risk of progression and death.