BACKGROUND: Health care system-wide outcomes from routine treatment with erlotinib and gefitinib are incompletely understood. OBJECTIVE: The aim of the study is to describe the effectiveness of erlotinib and gefitinib during the first decade of their routine use for treating advanced epidermal growth factor receptor (EGFR) mutation-positive nonsquamous non-small cell lung cancer in the entire cohort of patients treated in Aotearoa New Zealand. METHODS: Patients were identified, and data collated from national pharmaceutical dispensing, cancer registration, and mortality registration electronic databases by deterministic data linkage using National Health Index numbers. Time-to-treatment discontinuation and overall survival were measured from the date of first dispensing of erlotinib or gefitinib and analyzed by Kaplan-Meier curves. Associations of treatment outcomes with baseline factors were evaluated using univariable and multivariable Cox regressions. RESULTS: Overall, 752 patients were included who started treatment with erlotinib (n=418) or gefitinib (n=334) before October 2020. Median time-to-treatment discontinuation was 11.6 (95% CI 10.8-12.4) months, and median overall survival was 20.1 (95% CI 18.1-21.6) months. Shorter time-to-treatment discontinuation was independently associated with high socioeconomic deprivation (hazard ratio [HR] 1.3, 95% CI 1.1-1.5 compared to the New Zealand Index of Deprivation 1-4 group), EGFR L858R mutations (HR 1.3, 95% CI 1.1-1.6 compared to exon 19 deletion), and distant disease at cancer diagnosis (HR 1.4, 95% CI 1.2-1.7 compared to localized or regional disease). The same factors were independently associated with shorter overall survival. Outcome estimates and predictors remained unchanged in sensitivity analyses. CONCLUSIONS: Outcomes from routine treatment with erlotinib and gefitinib in New Zealand patients with advanced EGFR-mutant nonsquamous non-small cell lung cancer are comparable with those reported in randomized trials and other health care system-wide retrospective cohort studies. Socioeconomic status, EGFR mutation subtype, and disease extent at cancer diagnosis were independent predictors of treatment outcomes in that setting.