BACKGROUND: Using risk stratification approaches to determine eligibility has the potential to improve efficiency of screening. OBJECTIVES: To compare the public acceptability and potential impact on uptake of using different approaches to determine eligibility for screening. DESIGN: An online population-based survey of 668 adults in the UK aged 45-79 including a series of scenarios in the context of a potential kidney cancer screening programme in which eligibility was determined by age, sex, age and sex combined, a simple risk score (age, sex, body mass index, smoking status), a complex risk score additionally incorporating family history and lifestyle, or a genetic risk score. OUTCOME MEASURES: We used multi-level ordinal logistic regression to compare acceptability and potential uptake within individuals and multivariable ordinal logistic regression differences between individuals. RESULTS: Using sex, age and sex, or the simple risk score were less acceptable than age (P < .0001). All approaches were less acceptable to women than men. Over 70% were comfortable waiting until they were older if the complex risk score or genetics indicated a low risk. If told they were high risk, 85% would be more likely to take up screening. Being told they were low risk had no overall influence on uptake. CONCLUSIONS: Varying the starting age of screening based on estimated risk from models incorporating phenotypic or genetic risk factors would be acceptable to most individuals and may increase uptake. PATIENT OR PUBLIC CONTRIBUTION: Two members of the public contributed to the development of the survey and have commented on this paper.