Objective: The purpose of this study was to examine the mediating role of school adjustment in the relationship between adolescents’ mastery goal orientation and life satisfaction, and the differences according to gender in the relationship. Methods: The participants were 1,947 students from the 3rd, 4th, and 5th waves of the Korean Child Youth Panel Study(KCYPS). The data were analyzed with structural equation modeling(SEM) and multiple group analysis. Results: First, school adjustment of 1st graders in middle school mediated the relation between mastery goal orientation of 6th graders in elementary school and life satisfaction of 2nd graders in middle school. Second, the differences in gender were confirmed. The effect of mastery goal orientation of 6th graders in elementary school on school adjustment of 1st graders in middle school is higher for boys. In contrast, the effect of school adjustment of 1st graders in middle school on life satisfaction of 2nd graders in middle school is higher for girls. Conclusion/Implications: The results of this study suggested that mastery goal orientation before entering middle school and school adjustment after entering middle school could be important variables to increase adolescents’ life satisfaction. Also, it is necessary to consider gender difference for long-term intervention for improving adolescent life satisfaction.