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Summary: Background: Primary prevention of cardiovascular disease (CVD) is guided by risk-prediction tools, but these rarely account for the risk of dying from other conditions (ie, competing mortality risk). In England and Wales, the recommended risk-prediction tool is QRISK2, and a new version (QRISK3) has been derived and internally validated. We aimed to externally validate QRISK3 and to assess the effects of competing mortality risk on its predictive performance. Methods: For this retrospective population cohort study, we used data from the Clinical Practice Research Datalink. We included patients aged 25–84 years with no previous history of CVD or statin treatment who were permanently registered with a primary care practice, had up-to-standard data for at least 1 year, and had linkage to Hospital Episode Statistics discharge and Office of National Statistics mortality data. We compared the QRISK3-predicted 10-year CVD risk with the observed 10-year risk in the whole population and in important subgroups of age and multimorbidity. QRISK3 discrimination and calibration were examined with and without accounting for competing risks. Findings: Our study population included 1 484 597 women with 42 451 incident CVD events (4·9 cases per 1000 person-years of follow-up, 95% CI 4·89–4·99), and 1 420 176 men with 53 066 incident CVD events (6·7 cases per 1000 person-years, 6·66–6·78), with median follow-up of 5·0 years (IQR 1·9–9·2). Non-CVD death rose markedly with age (0·4% of women and 0·5% of men aged 25–44 years had a non-CVD death vs 20·1% of women and 19·6% of men aged 75–84 years). QRISK3 discrimination in the whole population was excellent (Harrell's C-statistic 0·865 in women and 0·834 in men) but was poor in older age groups (