 Relative net risks arise when the risks of a research intervention are justified by its potential clinical benefits, but the intervention’s risk-benefit profile is less favorable than the risk-benefit profile of one or more available alternatives. Imagine that investigators propose a randomized, controlled trial to compare an inexpensive drug against an expensive and somewhat more effective drug. Such trials make sense when, in the absence of a direct comparison, it is unclear whether the increased effectiveness of the more expensive drug justifies its costs. In this case, receipt of the cheaper drug would be contrary to participants’ interest in comparison to receiving the more expensive drug. The trial thus poses relative net risks to participants.