Aim: To investigate the factors associated with treatment selection and overall survival for first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs) therapy among patients with non-small-cell lung cancer. Materials & methods: We conducted a retrospective cohort study of linked administrative health databases in Ontario, Canada. Results: A total of 1011 patients received an EGFR-TKI as first-line therapy. Treatment selection and overall survival associated with these treatments were affected by age, sex, geographical residency, comorbidities and different sites of metastasis. Conclusion: Though recent approval of osimertinib offers a potential new standard of care in the first-line setting, earlier generation TKIs remain pillars in treatment of non-small-cell lung cancer therapeutic armamentarium. Our findings may contribute to optimizing treatment sequencing of EGFR-TKIs to maximize clinical benefits.