Current guidance around the prevention of cardiovascular events is based on long-term risk, typically calculated over 10 years. A growing body of evidence, however, suggests that vascular risk fluctuates greatly over much shorter time periods. We suggest a new paradigm for cardiovascular risk management that is based on targeting interventions during periods of enhanced risk. During such high-risk time windows, prophylactic therapy could have a disproportionately large absolute benefit, altering the risk-benefit balance and cost-effectiveness of available treatments. Major surgery is an example of an exposure known to lead to a transient increase in vascular risk. Emerging evidence supports the usefulness of short-term preventative interventions in the perioperative period. Influenza infection is another exposure known to increase the risk of vascular events, and cardiovascular mortality and morbidity are likely to be major features associated with pandemic influenza. Important questions remain, however, before preventative interventions can be offered as a routine part of influenza management.