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Summary: Background: Evidence-based guidelines recommend chemotherapy for medically fit patients with stages II–IV non-small cell lung cancer (NSCLC). Adherence to chemotherapy guidelines has rarely been studied among large populations, mainly because performance status (PS), a key component in assessing chemotherapy appropriateness, is missing from claims-based datasets. Among a large cohort of patients with known PS, we describe first line chemotherapy use relative to guideline recommendations and identify patient factors associated with guideline concordant use. Patients and methods: Insured patients, ages 50+, with stages II–IV NSCLC between 2000 and 2007 were identified via tumor registry (n =406). Chart abstracted PS, automated medical claims, Census tract information, and travel distance were linked to tumor registry data. Chemotherapy was considered appropriate for patients with PS 0–2. Multivariate logit models were fit to evaluate patient characteristics associated with chemotherapy over- and under-use per guideline recommendations. Tests of statistical significance were two sided. Results: Overall compliance with first line chemotherapy guidelines was 71%. Significant (p <0.05) predictors of chemotherapy underuse (19%) included increasing age (odds ratio [OR], 1.09), higher income (OR, 1.02), diagnosed before 2003 (OR, 2.05), and vehicle access (OR, 6.96) in the patient''s neighborhood. Significant predictors of chemotherapy overuse (10%) included decreasing age (OR, 0.92), diagnosed after 2003 (OR, 3.24), and higher income (OR, 1.05) in the patient''s neighborhood. Among NSCLC patients 29% do not receive guideline recommended chemotherapy treatment missing opportunities for cure or beneficial palliation, or receiving chemotherapy with more risk of harm than benefit. Care concordant with guidelines is influenced by age, economic considerations such as income and transportation barriers. [ABSTRACT FROM AUTHOR]