Objectives: To estimate the potential impact of universal screening for primary prevention of cardiovascular disease (National Health Service Health Checks) on disease burden and socioeconomic inequalities in health in England, and to compare universal screening with alternative feasible strategies. Design: Microsimulation study of a close-to-reality synthetic population. Five scenarios were considered: baseline scenario, assuming that current trends in risk factors will continue in the future; universal screening; screening concentrated only in the most deprived areas; structural population-wide intervention; and combination of population-wide intervention and concentrated screening. Setting: Synthetic population with similar characteristics to the community dwelling population of England. Participants: Synthetic people with traits informed by the health survey for England. Main outcome measure: Cardiovascular disease cases and deaths prevented or postponed by 2030, stratified by fifths of socioeconomic status using the index of multiple deprivation. Results: Compared with the baseline scenario, universal screening may prevent or postpone approximately 19.000 cases (interquartile range 11,000-28,000) and 3000 deaths (−1000-6000); concentrated screening 17,000 cases (9000-26.000) and 2000 deaths (−1000-5000); population-wide intervention 67,000 cases (57,000-77,000) and 8000 deaths (4000-11,000); and the combination of the population-wide intervention and concentrated screening 82,000 cases (73,000-93,000) and 9000 deaths (6000-13,000). The most equitable strategy would be the combination of the population-wide intervention and concentrated screening, followed by concentrated screening alone and the population-wide intervention. Universal screening had the least apparent impact on socioeconomic inequalities in health. Conclusions: When primary prevention strategies for reducing cardiovascular disease burden and inequalities are compared, universal screening seems less effective than alternative strategies, which incorporate population-wide approaches. Further research is needed to identify the best mix of population-wide and risk targeted CVD strategies to maximise cost effectiveness and minimise inequalities.