Background: In the ADAURA trial, adjuvant (adj) osimertinib improved disease free survival (DFS) in resected, EGFR-mutant (EGFRm) Stage IB-IIIA NSCLC compared to placebo. Based on these results, the FDA approved osimertinib in the adj setting. In this study, we have evaluated the hypothetical clinical and financial effects of adj osimertinib on the early-stage, EGFRm NSCLC patients at Cleveland Clinic who were treated prior to the FDA approval. Methods: Starting in 2010, Cleveland Clinic has been performing targeted molecular testing in all resected NSCLCs. With this information, we created a database of patients from 01/2010 to 01/2021 with resected, non-squamous NSCLC. The standard of care (SOC) arm of this study consisted of patients with stage IB-IIIA, EGFRm disease from our internal database. Data for the adj osimertinib arm were obtained through a microsimulation study by first generating the per-stage DFS distribution in the SOC arm, and then applying the per-stage hazard ratios from ADAURA to obtain the parameters of the exponential DFS distribution with osimertinib treatment. Outcomes and costs, such as treatment and imaging, were directly calculated for the SOC arm based on the amount of time each patient spent in a recurrence-free or recurrent state, and whether there was CNS involvement at recurrence. Costs and outcomes were averaged across 1000 simulated datasets for the osimertinib arm. Based on ADAURA we assumed that 78.4%, 16.2%, and 5.4% of DFS events were CNS- recurrence, CNS+ recurrence, or death. Results: 1,487 patients were included in the database. 724 of these patients had stage IB-IIIA disease and EGFR testing. 82 patients were EGFRm+ (exon 19 deletion or the L858R mutation), and their survival outcomes were used in the SOC arm. At 5 years, 32 (39%) of the patients were alive and disease free. With the addition of adj osimertinib, an estimated average of 61 (71.4%) of patients would have been disease free and alive. This corresponds to an average improvement in 5-year DFS of 35.4%. The cost of testing all 724 patients would have been $2,865.80 per patient eligible for osimertinib with single-gene EGFR testing or $5,279.11 per eligible patient with targeted NGS testing. The total treatment and healthcare costs with adj osimertinib in the 82 patients would have been $49,057,952.75 or $598,267.72 per patient. With SOC (surveillance +/- adj chemotherapy + osimertinib only upon recurrence), total and per patients costs were $12,297,374.11 and $149,967.98 respectively. This corresponds to an average increase in total costs of $448,299.74 per person with the use of adj osimertinib. Conclusions: Over a decade at Cleveland Clinic, about 5.5% (82/1,487) patients with early stage NSCLC would have been affected by the adj osimertinib approval. In our simulation, we estimated adj osimertinib would have improved 5-year DFS by 35.4% (29 more patients) but with a significant financial cost of about $450,000 per eligible patient.