Challenging behavior tends to increase in levels during adolescence for individuals with developmental disabilities (DD). If not addressed, this can lead to negative post-school outcomes for adolescents with DD. The purposes of this meta-analysis were to examine the effects of behavioral intervention in reducing challenging behaviors of adolescents with DD and to identify variables that could potentially moderate these effects. This meta-analysis included thirty single-case design studies that met standards for methodological rigor and experimental control. Overall, behavioral interventions were found to yield moderate effects for adolescents with DD (overall Tau-U = 0.68, SD = 0.04, [0.62, 0.73]) across settings and types of challenging behaviors. With regards to participant and setting characteristics, verbal ability and classroom setting were found to moderate the effects of the intervention outcomes with statistical significance. No other variables produced similar findings. Furthermore, statistically significant differences were found between interventions that included or did not include planned reinforcement as an intervention component. Several implications for research and practice are discussed.