The Centers for Medicare and Medicaid Services stopped reimbursing hospitals for additional costs associated with certain preventable adverse events in 2008. Despite the widespread controversy engendered by this policy, the actual financial effect has been small, leading to calls for expansion of the policy. This actuarial study used a case-control approach to estimate the annual marginal cost of preventable adverse events in hospitalized patients at $17.1 billion, largely attributable to post-surgical complications, health care–associated infections, and pressure ulcers. Never events accounted for approximately $3.7 billion in excess costs. The results of this study provide targets for policy efforts to control health care costs and improve patient safety.