This study assessed the efficacy of a co-designed, school-based intervention meant to promote physical activity and fitness among Dutch prevocational secondary students. In a two-year clustered randomized controlled trial, students’ physical activity and fitness was measured by indirect and direct methods. In the intervention group, we used the triple-I procedure, a participatory action research method, to co-design the intervention together with the students and schools. This procedure involved focus group discussions by interviewing and imaging techniques, followed by a co-design process to align the intervention content and implementation processes with students’ preferences. The study involved 22 Dutch schools, with a total of 2685 13-to-14-year-old prevocational secondary students. Schools were randomly assigned to either intervention (11 schools, 1446 students) or control group (11 schools, 1239 students).There were no significant intervention differences between students’ overall physical activity behavior on intervention versus control schools. However, with regards to various specific physical fitness indicators, such as the long jump, handgrip strength, shuttle run test, and the sum of skinfolds, intervention school students performed significantly better than the control group students. Furthermore, when taking into account student participation, i.e. the success of the co-design process, schools with higher levels of student participation showed higher shuttle run scores. However, such graded effects were not similarly apparent with regards to students’ physical fitness indicators. This study showed that co-designing a comprehensive physical activity intervention on numerous Dutch high schools via the Triple-I Interactive Method was feasible. Moreover, results showed that certain aspects of physical fitness were improved after two years of intervention, although taken together with the lack of effects on physical activity, results were mixed. The trial was registered as ISRCTN35992636 of the ISRCTN ...