The objectives of this systematic review were to summarize the available evidence on the effects of prevention and intervention programs aimed at primary and secondary students for increasing school completion or reducing school dropout. The primary focus of the meta-analysis was to examine the comparative effectiveness of different programs and program approaches in an effort to identify those with the largest and most reliable effects on school completion and dropout outcomes. The authors also sought to summarize the effects of programs designed for pregnant and parenting teens. A comprehensive and diverse international search strategy was used to locate qualifying studies reported between 1985 and 2010. A wide range of electronic bibliographic databases were searched, along with research registers, other grey literature databases, reference lists of all previous meta-analyses and reviews on the topic, as well as citations in research reports. The authors also maintained correspondence with researchers in the field of school dropout prevention. The literature search yielded a total of 23,677 reports, 2,794 which were deemed potentially relevant and retrieved for eligibility determination. Of those, 548 reports describing 167 different studies were included in the final review. Random-effects inverse variance weighted meta-analytic methods were used to synthesize odds ratios for the school dropout outcomes. Meta-regression models were used to examine the effects of program characteristics, methodological characteristics, and participant characteristics on the dropout odds ratios. Funnel plots, regression tests for small sample bias, and trim and fill analyses were used to assess the possibility of publication bias. Overall, results indicated that most school- and community-based programs were effective in decreasing school dropout. Given the minimal variation in effects across program types, the main conclusion from this review is that dropout prevention and intervention programs, regardless of type, will likely be effective if they are implemented well and are appropriate for the local environment. The authors recommend that policy makers and practitioners choosing dropout prevention programs consider the cost-effectiveness of programs, and choose those that fit best with local needs as well as implementer abilities and resources. Appended are: (1) Additional Tables; and (2) Additional Figures. (Contains 11 tables, 5 figures and 3 footnotes.) [Funding for this paper was provided by the Peabody Research Institute, Vanderbilt University.]