BACKGROUND: Environmental tobacco smoke (ETS) negatively affects children with asthma. The prevalence of ETS exposure among children with poor asthma control may be changing. Importantly, the mechanisms by which ETS worsens asthma control are poorly understood. OBJECTIVE: We describe how ETS affects gastroesophageal reflux (GER), respiratory infections, and leukotriene production among children with poor asthma control. METHODS: We analyzed data from 306 children between 6 and 17 years of age with poorly controlled asthma enrolled in a 6-month clinical trial. We evaluated prevalence and determinants of ETS exposure by interview, questionnaire, and urinary cotinine and the association of ETS exposure on leukotriene production, respiratory infections, GER, lung function, and asthma control. We used multivariable linear, logistic, and Poisson regressions to assess outcomes. RESULTS: ETS prevalence estimates ranged from 6% to 30%. Children with domestic indoor exposure had worse asthma control (c-Asthma Control Test, 17.8 vs 21.5; P = .04), worse FEV1 % predicted (84.1 vs 90.7; P = .02), and a trend for increased mean urinary leukotriene E4. ETS from any setting was associated with increased symptomatic respiratory infections (adjusted incidence rate ratio: 1.30; P = .02). However, children exposed to ETS did not have symptoms or pH probe results, suggestive of heightened GER. CONCLUSIONS: Domestic smoking exposure was associated with both higher rates of symptomatic respiratory infection and poorer asthma control despite generally intensive controller therapy. ETS exposure is common among asthmatic children with poor control and may worsen asthma control by promoting respiratory infections. Further investigation is required to elucidate ETS mechanisms in poor asthma control.