Background: For patients (pts) with advanced non-small cell lung cancer (NSCLC) treated with front line immunotherapy-based treatment, the optimal duration of immune checkpoint inhibitor (ICI) treatment is unknown. We aimed to assess practice patterns surrounding ICI treatment discontinuation at two years, and to evaluate association of duration of therapy with overall survival by comparing pts who received fixed duration ICI therapy for 2 years vs those who continued therapy beyond two years. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database, and included adult pts diagnosed with advanced NSCLC from 2016-2020, who received frontline immunotherapy-based treatment. Pts who were still on treatment without progression at 2 years were classified as “fixed duration” (treatment discontinuation at 2 years, between 700-760 days) vs “indefinite duration” (continued treatment beyond two years, > 760 days). Overall survival from 760 days was analyzed using Kaplan-Meier methodology. Multivariable Cox regression adjusted for patient and cancer-specific factors was used to compare survival between fixed and indefinite-duration groups. Results: Our analytic cohort consisted of 113 pts in the fixed duration group and 593 in the indefinite duration group; median age was 69, 49% were female, and 71% were White. Pts in the fixed duration group were more likely to have a history of smoking and be treated at an academic center. There was no significant difference in overall survival between pts in the fixed duration and indefinite duration groups, either on univariable (HR 1.26, 95% CI 0.77-2.08) or multivariable Cox regression (HR 1.33, 95% CI 0.78-2.25). Conclusions: In a real world cohort of advanced NSCLC pts treated with front line ICI, only about 1 in 5 stopped treatment at two years rather than continuing treatment beyond two years. The lack of significant overall survival advantage for the indefinite duration cohort on adjusted analysis provides reassurance to pts and providers who wish to stop therapy at 2 years.