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Background: Increased cigarette costs have inadvertently strengthened the appeal of discounted brands to price-sensitive smokers. Although smokers perceive discounted brands as having poorer quality, little is known about their delivery of toxic tobacco smoke constituents compared with premium-branded tobacco products. Methods: We investigated the differences between discount and premium brand smokers using the National Health and Nutrition Examination Survey 2011-2012 Special Smoker Sample. Our analyses focused on demographic differences and 27 biomarkers of harmful and potentially harmful constituents (HPHC) listed by the FDA, including volatile organic compounds, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronide; reported as total NNAL (tNNAL)], metals, and polycyclic aromatic hydrocarbons (PAHs). Data were analyzed using linear regression models adjusting for potential confounders. Results: A total of 976 non-tobacco users and 578 recent cigarette smokers were eligible for analysis, of which 141 (26.0% weighted) smoked discount brand cigarettes and 437 (74.0% weighted) smoked premium. Discount brand smokers were older, predominantly non-Hispanic white, and had higher serum cotinine. Discount brand smokers had significantly higher levels of 13 smoking-related biomarkers, including tNNAL, uranium, styrene, xylene, and biomarkers of exposure to PAHs (naphthalene, fluorene, and phenanthrene), compared with premium brand smokers. Conclusions: These findings suggest that discount cigarette use is associated with higher exposure to several carcinogenic and toxic HPHCs. Impact: These results may have important regulatory implications for product standards, as higher exposures could lead to a greater degree of harm. Cancer Epidemiol Biomarkers Prev; 27(5); 601-9. ©2018 AACR ., (©2018 American Association for Cancer Research.)