BACKGROUND:The directionality of the association of physical activity (PA) and sedentary behaviour (SB) with health-related quality of life (HRQoL) remains unknown in adolescents. This study aimed to investigate the association of 2-year cumulative level of PA and SB with HRQoL and the reverse association.METHODS:We included 1445 adolescents in France from a 2-year longitudinal study with three follow-up times (PRALIMAP trial). At each follow-up, adolescents completed the International Physical Activity Questionnaire for PA and SB and the Duke Health Profile for HRQoL. Statistical analyses involved linear and logistic regressions adjusted for socio-demographic characteristics.RESULTS:The cumulative number of times an adolescent achieved the PA recommendations during the 2 years was associated with better physical, mental, social and general HRQoL (p for trend < 0.0001). In contrast, high SB predicted low HRQoL for most dimensions except social HRQoL (p = 0.12). Combining PA and SB, the effect of recommended PA on HRQoL was offset in part by high SB. In the reverse association, high HRQoL predicted high PA (overall, vigorous, moderate and recommended PA), but was not associated with SB.CONCLUSIONS:The association between PA and HRQoL was cumulative and bidirectional among adolescents, whereas low HRQoL seemed to be a consequence of high SB rather than a cause (cumulative but not bidirectional). Promoting recommended PA and low SB may help improve HRQoL among adolescents, with a possible virtuous cycle with regard to PA.