Aims: Vigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity levels. There is a very limited understanding of the minimal and optimal amounts of vigorous physical activity in relation to mortality and disease incidence. Methods and results: A prospective study in 71 893 adults [median age (IQR): 62.5 years (55.3, 67.7); 55.9% female] from the UK Biobank cohort with wrist-worn accelerometry. VPA volume (min/week) and frequency of short VPA bouts (≤2 min) were measured. The dose-response associations of VPA volume and frequency with mortality [all-cause, cardiovascular disease (CVD) and cancer], and CVD and cancer incidence were examined after excluding events occurring in the first year. During a mean post-landmark point follow-up of 5.9 years (SD ± 0.8), the adjusted 5-year absolute mortality risk was 4.17% (95% confidence interval: 3.19%, 5.13%) for no VPA, 2.12% (1.81%, 2.44%) for >0 to <10 min, 1.78% (1.53%, 2.03%) for 10 to <30 min, 1.47% (1.21%, 1.73%) for 30 to <60 min, and 1.10% (0.84%, 1.36%) for ≥60 min. The ‘optimal dose’ (nadir of the curve) was 53.6 (50.5, 56.7) min/week [hazard ratio (HR): 0.64 (0.54, 0.77)] relative to the 5th percentile reference (2.2 min/week). There was an inverse linear dose-response association of VPA with CVD mortality. The ‘minimal’ volume dose (50% of the optimal dose) was ∼15 (14.3, 16.3) min/week for all-cause [HR: 0.82 (0.75, 0.89)] and cancer [HR: 0.84 (0.74, 0.95)] mortality, and 19.2 (16.5, 21.9) min/week [HR: 0.60 (0.50, 0.72)] for CVD mortality. These associations were consistent for CVD and cancer incidence. There was an inverse linear association between VPA frequency and CVD mortality. 27 (24, 30) bouts/week was associated with the lowest all-cause mortality [HR: 0.73 (0.62, 0.87)]. Conclusion: VPA of 15-20 min/week were associated with a 16-40% lower mortality HR, with further decreases up to 50-57 min/week. These findings suggest reduced health risks may be attainable through relatively modest amounts of VPA accrued in short bouts across the week. © 2022 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.