Background: In 2009, the Pennsylvania Department of Health developed the Active Schools Program (ASP) which required 30?minutes of daily physical education (PE) in middle schools to reduce childhood obesity. This investigation evaluated the ASP effects on physical fitness and weight status in middle school adolescents throughout 1 academic year. Methods: A quasi-experimental design was used to recruit middle schools into an intervention group (N?=?30) or control group (N?=?9). Results: Physical fitness outcomes had larger intervention effects than weight status outcomes. These effects were most profound among at-risk students. Multiple linear regression analysis provided a best-guess effect of daily PE on body mass index (BMI) percentile of -1.2, 95% confidence interval (CI) (-1.9, -0.5) for at-risk females and -0.8, 95% CI (-1.5, -0.1) for at-risk males. Much of this benefit is attributable to the differential increase in physical fitness achieved by students with the benefit of having daily PE. Conclusions: Thirty minutes of daily PE can be considered a scientific approach to ameliorate health outcomes in at-risk middle school adolescents, particularly among females. Improvements on BMI percentile among at-risk youth are presaged by greater improvements in physical fitness. This investigation supports a school-based approach aimed to improve behavioral risk factors as a means to reduce childhood obesity.