Cardiovascular screening has been shown to reduce mortality in trials involving men. This study evaluated the effect of cardiovascular screening in both sexes, with all-cause mortality as the primary outcome. The Viborg Screening Program, a prospective, population-based study in Denmark, in which the intervention consisted of inviting all 67-year olds to screening for carotid plaque, lower extremity artery disease, abdominal aortic aneurysm, hypertension, cardiac arrhythmia/ischaemia, and diabetes mellitus. This cohort included invitees from the first 5 years (2014-2019). Controls were 67-year olds without screening access. Effects were evaluated using propensity score matching (1:3 ratio, nearest-neighbour matching) and analysed using Cox proportional hazards models under the intention-to-invite principle. Sex-stratified analyses of all-cause mortality were conducted post hoc. Among 5505 invitees, three died before inclusion and 4602 participated (83.6%). Ninety individuals lacked registry information. After matching, 5412 invitees and 16 236 controls were included. During a median follow-up of 5.8 years, 372 (6.9%) invitees and 1444 (8.9%) controls died [hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.68-0.85; P < .001]. The number needed to invite to save one life was 49. The HR for cardiovascular mortality was 0.76 (95% CI 0.56-1.03), for major adverse cardiovascular events 1.10 (95% CI 1.01-1.19), and for major adverse limb events 0.70 (95% CI 0.50-0.98). All-cause mortality HRs were 0.73 (95% CI 0.63-0.84) for men, 0.82 (95% CI 0.68-0.98) for women, 0.70 (95% CI 0.61-0.80) for those without prior cardiovascular disease (CVD), and 0.97 (95% CI 0.78-1.21) for those with prior CVD. Multi-modality non-invasive cardiovascular screening reduced 5-year all-cause mortality among 67-year olds, also when stratified by sex. Prioritizing individuals without known CVD may enhance population-level impact.