Use of wearable devices that monitor physical activity is projected to increase more than fivefold per half-decade1. We investigated how device-based physical activity energy expenditure (PAEE) and different intensity profiles were associated with all-cause mortality. We used a network harmonization approach to map dominant-wrist acceleration to PAEE in 96,476 UK Biobank participants (mean age 62 years, 56% female). We also calculated the fraction of PAEE accumulated from moderate-to-vigorous-intensity physical activity (MVPA). Over the median 3.1-year follow-up period (302,526 person-years), 732 deaths were recorded. Higher PAEE was associated with a lower hazard of all-cause mortality for a constant fraction of MVPA (for example, 21% (95% confidence interval 4-35%) lower hazard for 20 versus 15 kJ kg-1 d-1 PAEE with 10% from MVPA). Similarly, a higher MVPA fraction was associated with a lower hazard when PAEE remained constant (for example, 30% (8-47%) lower hazard when 20% versus 10% of a fixed 15 kJ kg-1 d-1 PAEE volume was from MVPA). Our results show that higher volumes of PAEE are associated with reduced mortality rates, and achieving the same volume through higher-intensity activity is associated with greater reductions than through lower-intensity activity. The linkage of device-measured activity to energy expenditure creates a framework for using wearables for personalized prevention.TS, KW, SB, SJS, TL, PCD, MP, JJ and NJW are supported by the UK Medical Research Council (unit programme numbers MC_UU_12015/1 and MC_UU_12015/3). PCD is supported by a National Health and Medical Research Council of Australia research fellowship (#1142685). TL is supported by Cambridge Trust and St Catharine’s College
