Little is known about the feasibility and rapidity with which the academic learning of students who enter high school multiple years behind grade level can be accelerated. This study uses multiple regression analyses of standardized test and survey data from high-poverty high schools in two large urban districts to evaluate initial effects of the Talent Development High Schools (TDHS) ninth-grade instructional program in reading and mathematics. Pre-, post-, and match-control comparisons show that students in TDHS significantly outperformed students in the control schools in mathematics and reading. Supplemental surveys show a higher percentage of students in TDHS reported learning new skills, strategies, and concepts, and TDHS teachers indicated they were able to use a more varied set of activities during extended periods, use cooperative learning strategies, engage students in group projects, and have students present multiple solutions or methods and relate their academic work to real-world experiences and examples.