Background: Guidelines have evolved from 2011-2019; there are now 23 approved therapies targeting various predictive biomarkers in mNSCLC. 2021 NCCN Guidelines advocate for a minimum of ALK, EGFR, BRAF, METex14, NTRK1/2/3, RET, KRAS, and ROS1 testing before determining a treatment regimen. The study objective was to estimate the association between the presence of biomarker testing and smoking status, age, sex, race, ethnicity, histology, and diagnosis year in patients with mNSCLC. Methods: CLQD is a real-world data source that provides de-identified electronic health record (EHR) data from more than 60 U.S. oncology practices utilizing 10 different EHRs. This retrospective analysis included patients initially diagnosed with mNSCLC from January 1, 2011, to December 31, 2019. Standard logistic regression models were fit separately by practice to estimate practice-specific odds ratios to assess variability across practices in associations between covariates (smoking status, age, race, etc.) and the primary outcome of biomarker testing, defined as documented testing for EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, ERBB2, and/or PD-L1 within -60 to +365 days of mNSCLC diagnosis. Random effects logistic regression was then used to estimate associations with random intercepts, accounting for clustering by practices. Results are reported as odds ratios (OR) with 95% confidence intervals (CI). Results: 8704 patients from 31 practices were eligible. Testing rates increased from 31.5% in 2011 to a peak of 62.3% in 2017. Patients with a smoking history were half as likely to receive testing than patients without a smoking history (OR = 0.50, 95% CI: 0.41, 0.60); patients with unknown smoking history were 0.66 times as likely (95% CI: 0.52, 0.84). Females were more likely to be tested than males (OR = 1.19, 95% CI: 1.07, 1.32). After adjusting for other covariates, Asian patients were 1.51 times more likely to be tested than patients of other races (95% CI: 1.05, 2.17); Hispanic patients were 1.33 times more likely to be tested than patients without Hispanic ethnicity (95% CI: 0.99, 1.78). The odds of receiving biomarker testing were 6x greater for patients with non-squamous mNSCLC versus squamous mNSCLC (95% CI: 5.45, 7.20). Patients > 70 years old were less likely to be tested (OR = 0.83, 95% CI: 0.75, 0.93) than younger patients. Conclusions: Our data demonstrate annual increases in testing rates, reflecting guideline changes. However, in this cohort of patients with mNSCLC, biomarker testing was more likely for non-squamous mNSCLC patients, females, Asians, Hispanics, or those who did not have a history of smoking. Patient characteristics should no longer factor into obtaining biomarker testing. Non-discriminant, broad panel-based reflex molecular testing in mNSCLC can reduce treatment choice ambiguity and enhance patient opportunities.