The purpose of this research was to enhance self-efficacy beliefs, chemistry content, and pedagogical content knowledge of middle grades teachers by incorporating specific design elements into professional development. This study analyzed the influence of program design on achieving gains in personal science teaching self-efficacy, outcome expectancy, chemistry content, and pedagogical content knowledge in 4 discrete cohorts (N = 135). Significant changes were produced in self-efficacy at 0.01 in each cohort, personal science teaching self-efficacy was significantly enhanced in Cohorts 1, 2, and 4 at 0.01, and outcome expectancy was significantly enhanced in Cohorts 1 and 3 at 0.01 and in Cohort 4 at 0.05. Professional development that enhances personal science teaching self-efficacy and outcome expectancy should be recognized as essential to achieving scientific literacy for all students.