Numerous observational studies have shown that coronary artery calcium (CAC) imaging can improve cardiovascular risk assessment in asymptomatic adults. Whether CAC imaging can improve cardiovascular outcomes as part of an overall risk reduction strategy compared to alternative care approaches has not been demonstrated in clinical trials. Therefore, the role of CAC imaging in primary prevention of cardiovascular disease is somewhat contentious. Advocates for expanded CAC testing offer the large amount of observational data as support for their position, while opponents to wider CAC testing propose that only a clinical trial can resolve the matter. This paper reviews the arguments for and against such a trial based on clinical, safety and economic considerations. We also propose potential trial approaches based on recent changes in clinical practice that could make a new CAC trial design feasible.