Countries differ in using opt-in (informed consent) or opt-out (presumed consent) systems for donor registration. Using newly assembled cross-country panel data, this paper provides causal evidence that switching to a weak opt-out regime results in a negligible or even negative change in the rate of organ donation. A theoretical signaling model explains when opt-in or opt-out yields more donations, emphasizing the role of donation propensity, signaling costs, and the family’s ability to overturn defaults. A large laboratory experiment further tests these mechanisms, showing that opt-in often produces equal or higher donation. The results underscore that defaults alone rarely increase donations.