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RATIONALE Protective effects of a high quality diet on respiratory health, particularly among youths exposed to environmental tobacco smoke (ETS), are unknown. OBJECTIVES To assess if a higher quality diet is associated with improved respiratory symptoms and lung function among adolescents, and if these associations are modified by ETS exposure. METHODS This was a cross-sectional study on 7,026 nonsmoking adolescents of the 2003-2012 National Health and Nutrition Examination Survey. Diet quality was assessed using the Healthy Eating Index-2010 score (HEI-2010), categorized into quintiles. ETS exposure was measured using serum cotinine, dichotomized as high (>2.99 ng/ml) or low (≤2.99 ng/ml). Outcomes included the presence of wheezing and cough symptoms in the past 12 months, and in a sub-group, spirometric lung function. Survey-design adjusted logistic and linear models evaluated associations between diet and 1) respiratory symptoms and 2) lung function, respectively, and assessed the interaction between HEI-2010 and serum cotinine. RESULTS While there were no significant associations between diet quality and respiratory symptoms, there was a significant interaction between HEI-2010 and serum cotinine on wheezing (pint = 0.011). In models stratified by serum cotinine, adolescents with high serum cotinine and the healthiest diet (5th quintile HEI-2010) experienced lower wheezing odds (OR, 0.10; 95% CI, 0.02-0.61), compared to those with the poorest diet (1st quintile HEI-2010). In contrast, among adolescents with low serum cotinine, there were no significant differences in any respiratory symptoms between those with the highest, compared to the lowest diet quality. Of the sub-group with spirometry data (n = 3,166), there was a trend towards better lung function with improving diet quality, although this did not achieve statistical significance. There was no effect modification by ETS exposure on the relationship between diet quality and lung function. CONCLUSIONS Consuming a higher quality diet was associated with lower wheezing odds in adolescents with substantial ETS exposure. While longitudinal studies are needed, public health interventions to improve diet quality in vulnerable, environmentally-exposed populations merit consideration.