Background Obesity prevention among youth of low SES is a public health priority given the higher prevalence of youth obesity in this population subgroup. Purpose To evaluate the 24-month impact of a school-based obesity prevention program among adolescent girls living in low-income communities. Design The study was a school-based group RCT, the Nutrition and Enjoyable Activity for Teen Girls (NEAT Girls) intervention. Setting/participants The study involved 12 secondary schools located in low-income communities in New South Wales, Australia. Participants were 357 adolescent girls (aged 13.2±0.5 years). Intervention The 12-month multicomponent intervention was guided by social cognitive theory and involved strategies to promote physical activity, reduce sedentary behaviors, and improve dietary outcomes. Main outcome measures The primary outcome was BMI, and secondary outcomes were BMI z-score; percentage body fat (bioelectrical impedance analysis); physical activity (accelerometers); dietary intake; and recreational screen-time (self-report). Data were collected in 2010–2012 and analyzed in 2012. Results After 24 months, there were no intervention effects on BMI (adjusted mean difference −0.33, 95% CI= −0.97, 0.28, p=0.353) and BMI z-score (−0.12, 95% CI= −0.27, 0.04, p=0.178). However, there was a group-by-time interaction for percentage body fat (−1.96%, 95% CI= −3.02, −0.89, p=0.006). Intervention effects for physical activity, screen time, and dietary intake were not significant. Conclusions The NEAT Girls intervention did not result in effects on the primary outcome. Further study of youth who are “at risk” of obesity should focus on strategies to improve retention and adherence in prevention programs.