INTRODUCTION: Adolescent knee pain is considered benign and presumed to disappear without treatment. However, this has never been investigated. The purpose of this study was to 1) compare leisure time sports participation, health-related quality of life (HRQoL) and body mass index between adolescents with and without self-reported knee pain, 2) investigate how many adolescents still have knee pain after one year and 3) identify risk factors for one-year persistence of knee pain. MATERIAL AND METHODS: The design was a prospective cohort study and a nested case-control study. In September 2011, a total of 768 adolescents between 12-15 years of age from schools in the municipality of Aalborg answered a questionnaire on demographics, sports participation, current pain and HRQoL. After one year, adolescents who reported knee pain at first contact were again contacted by telephone and asked if they experienced knee pain. RESULTS: At first contact, 215 adolescents reported knee pain. Adolescents with knee pain had a significantly higher leisure time sports participation level and a lower HRQoL than adolescents without knee pain. 48.8% (n = 80) still reported knee pain after one year. Female gender, taking part in sports more than twice weekly, lower HRQoL and daily knee pain increased the risk of reporting knee pain after one year. CONCLUSION: Adolescents with self-reported knee pain participate in more leisure time sports and have a lower HRQoL than adolescents without knee pain. 50% had persistent long-lasting knee pain, and a higher frequency of leisure time sports participation increased the risk of reporting knee pain after one year. FUNDING: Danish Rheumatism Association, The Association of Danish Physiotherapists Research Fund and The Obel Family Foundation. None of the funders have any role in the study other than to provide funding. TRIAL REGISTRATION: Ethical approval was obtained from the local ethics committee in the North Denmark Region (N-20110020).