Despite widespread recognition among policy makers, educational leaders, and the nation as a whole of the importance of science, engineering, and technology as drivers of the future of the country and society, the science achievement of America's students is mediocre at best, in comparison to that of international peers. On the 2012 PISA tests in science, U.S. 15-year-olds ranked 28th, slightly below the average of the 65 participating countries. On the 2011 National Assessment of Educational Progress science assessment, 68% of eighth graders scored below "proficient." In recent years, there has been growing consensus about the goals of science education in elementary and secondary schools, and an acceleration in the use of rigorous quantitative methods to evaluate innovative science methods. The intention of this review is to place all types of programs designed to enhance the science achievement of middle and high school students on a common scale, to provide educators with meaningful, unbiased information that they can use to select programs most likely to make a difference for their students' learning. In addition, the review is intended to look broadly for common factors that might underlie effective practices across programs and program types, and to inform an overarching understanding of effective instruction in secondary science. A total of 21 qualifying studies based on over 31,000 students in grades 6-12 met the inclusion criteria. Ten studies were quasi-experiments (including randomized quasi-experiments) and 11 were randomized studies. Findings were reported in 16 published articles and five in unpublished documents such as dissertations and technical reports. Two of the studies were published in the 1990s, 8 in the 2000s, and 11 in the 2010s. A broad literature search was carried out in an attempt to locate every study that could possibly meet the inclusion requirements. A meta-analysis calculated outcomes in effect sizes, and these were pooled within well-justified categories. Electronic searches were made of educational using different combinations of key words and the years 1990-2015. Twenty-one studies met inclusion criteria including use of randomized or matched assignment to conditions, measures that assess content emphasized equally in experimental and control groups, and a duration of at least 12 weeks. Outcomes support the use of programs with a strong focus on professional development, technology, and support for teaching, rather than materials-focused innovations. The types of programs that make a difference in student outcomes are those that help teachers teach more effective lessons: technology designed primarily to help students visualize science concepts, and instructional process models that provide teachers with extensive professional development to help them apply strategies such as cooperative learning, use of metacognitive skills, and science-literacy integration.