This study analyses the effects of group differentiation by students' learning strategies of around 1200 students in 46 classes from eight secondary schools in the Netherlands. In an experimental setup with randomization at the class level, division of students over three groups per class (an instruction-independent group, an average group, and an instruction-dependent group) is based on learning strategies, measures using the Motivated Strategies for Learning Questionnaire (MSLQ). Each group is offered instruction fitting their own learning strategy. The results show that student performance is higher in classes where the differentiation was applied, and that these students score higher at some scales of the posttest of the questionnaire on motivation, metacognition and self-regulation. However, there are differences between classrooms from different teachers. Additional teacher questionnaires confirm the discrepancy in teacher attitudes towards the intervention.