Introduction Secondhand smoke (SHS) exposure causes disease and death among nonsmokers. With a plethora of smoke-free legislation implemented and a steady decrease in cigarette consumption noted over the past decade in the U.S., this study assessed trends in indoor SHS exposure among U.S. adolescents in grades 6–12 during 2000–2009. Methods Data were obtained from the 2000–2009 National Youth Tobacco Survey – a national survey of U.S. middle and high school students. SHS exposure within an indoor area within the past seven days was self-reported. Trends in indoor SHS exposure during 2000–2009 were assessed overall and by socio-demographic characteristics, using the Wald's test in a binary logistic regression. Within-group comparisons were performed using chi-squared statistics (p<0.05). Results The proportion of U.S. middle and high school students who were exposed to indoor SHS declined from 65.5% in 2000 to 40.5% in 2009 (p<0.05 for linear trend). Significant declines were also observed across all population subgroups. Between 2000 and 2009, prevalence of indoor SHS exposure declined significantly among both middle (58.5% to 34.3%) and high school (71.5% to 45.4%) students. Prevalence of indoor SHS exposure was significantly higher among girls (44.0% in 2009) compared to boys (37.2% in 2009) during each survey year. Similarly, prevalence of indoor SHS exposure during 2000–2009 was highest among non-Hispanic whites (44.2% in 2009) and lowest among non-Hispanic Asians (30.2% in 2009). During each survey year, prevalence was highest among the oldest age group (≥18 years) and lowest among the youngest (9–11 years). Also, prevalence was significantly higher among current cigarette smokers (83.8% in 2009) compared to nonsmokers (34.0% in 2009). Conclusion Significant declines in indoor SHS exposure among U.S. middle and high school students occurred during 2000–2009. While the results are encouraging, additional efforts are needed to further reduce youth indoor SHS exposure.