Abstract Aims The interplay between physical activity (PA) volume and intensity is poorly understood in relation to cardiovascular disease (CVD) risk. This study aimed to investigate the role of PA intensity, over and above volume, in relation to incident CVD. Methods and results Data were from 88 412 UK Biobank middle-aged adults (58% women) without prevalent CVD who wore accelerometers on their dominant wrist for 7 days, from which we estimated total PA energy expenditure (PAEE) using population-specific validation. Cox proportional hazards regressions modelled associations between PAEE (kJ/kg/day) and PA intensity (%MVPA; the fraction of PAEE accumulated from moderate-to-vigorous-intensity PA) with incident CVD (ischaemic heart disease or cerebrovascular disease), adjusted for potential confounders. There were 4068 CVD events during 584 568 person-years of follow-up (median 6.8 years). Higher PAEE and higher %MVPA (adjusted for PAEE) were associated with lower rates of incident CVD. In interaction analyses, CVD rates were 14% (95% confidence interval: 5–23%) lower when MVPA accounted for 20% rather than 10% of 15 kJ/kg/d PAEE; equivalent to converting a 14 min stroll into a brisk 7 min walk. CVD rates did not differ significantly between values of PAEE when the %MVPA was fixed at 10%. However, the lowest CVD rates were observed for combinations of both higher PAEE and %MVPA. Conclusion Reductions in CVD risk may be achievable through higher PA volume and intensity, with the role of moderately intense PA appearing particularly important. This supports multiple approaches or strategies to PA participation, some of which may be more practical or appealing to different individuals.