BACKGROUND:The directionality of the associations of domain-specific physical activity (PA) and sedentary behaviour (SB) with health-related quality of life (HRQoL) in adults remain insufficiently known. This study investigated the longitudinal associations of 10-year cumulative levels of PA and SB with HRQoL and the reverse associations.METHODS:A sample of 2093 (47.8% men) participants from a cohort of French adult (SU.VI.MAX) was included. Data were collected at 3 time points (1998, 2001 and 2007) using the Modifiable Activity Questionnaire (MAQ) for PA (leisure-time and occupational) and SB (screen-viewing, reading and total sitting time) and the DUKE Health Profile for HRQoL. The cumulative level (from 0 to 3) referred to the number of time points where a high PA level, high SB or good HRQoL was reported. Regression models examined the 10-year cumulative level of PA, SB as predictors of HRQoL and reverse associations.RESULTS:The 10-year cumulative level of high PA, both leisure-time and occupational, predicted a higher HRQoL while the 10-year cumulative level of high screen-viewing time and high total sitting time was associated with lower HRQoL. For the reverse association, cumulative level of good HRQoL predicted more leisure-time PA, less screen-viewing time and less total sitting time but was not related to occupational PA.CONCLUSION:Relationships between PA, SB and HRQoL are complex and should not be oversimplified in one or the other direction. Taking into account domain-specific PA and SB in health promotion programs appears of prime importance to design interventions aiming at improving HRQoL.