PURPOSE: School-based physical activity (PA) has mostly been examined in a preventive perspective. The purpose of this study was to examine the changes in physical activity, physical fitness and psychosocial well-being in early adolescents after the implementation of a school-based health promotion program in secondary school. METHODS: Four municipalities with 15 secondary schools in Telemark County, Norway, were recruited into an intervention or a control group. A total of 644 pupils participated in the study (response rate: 79%). The schools in the intervention group implemented the Active Healthy Kids program, where the physical activity component consisted of: (1) 120 min/week of physically active lessons (PAL), (2) 25 min/week of physical active breaks during classroom lessons and (3) 135 min/week of curriculum based normal physical education. Primary outcome was physical activity assessed by accelerometer and expressed as counts per minutes. Secondary outcomes were sedentary time, physical fitness, vitality, school effort and health-related quality of life in the five domains; physical health, psychological wellbeing, parent, peers and school environment. RESULTS: There was a Group X Time effect for school-based, but not full-day, physical activity (p=0.005), and for cardiorespiratory fitness (p=0.02) and vitality (p=0.008). A Group effect was found for the perceived exerted effort in class (p<0.001) and the health-related quality of life domains “psychological well-being” (p=0.04) and “school environment” (p<0.001). CONCLUSIONS: A multi-component, school-based, health-promotion intervention with emphasis on the use of PAL led to positive changes in school-based physical activity, cardiorespiratory fitness, vitality and health-related quality of life among early adolescents in a county with poor public health profile. This might have implications for the development and promotion of general health and well-being throughout adolescence. Trial registration: Approved by the Norwegian Data Protection Services (ID 54327), and registered in ClinicalTrials.gov, (ID NCT03906851).