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Objective: To reduce uncertainty about the effectiveness of Departments of Motor Vehicles (DMV) interventions, we assessed the influence of several DMV-based media campaigns on organ donor registration., Method: Across 4 studies, campaigns were implemented in 8 (Studies 1-3) or 9 (Study 4) New Mexico DMVs. Three theories guided message development (i.e., efficacy, altruism, vested interest). Donor registration was the outcome measure., Results: In Study 1, both the efficacy (OR = 1.14) and altruism (OR = 1.11) campaigns resulted in significantly more registrations than the control condition and the vested interest campaign. In Study 2, the efficacy campaign (OR = 1.13) again resulted in significantly more registrations than the control and vested interest campaign. In Study 3, a new version of the efficacy campaign (OR = 1.21) and 2 new versions of the vested interest campaigns (OR = 1.12; 1.14) all resulted in significantly more registrations than the control condition. In Study 4, neither the efficacy campaign (OR = 1.06) nor a campaign that combined efficacy and vested interest materials (OR = 1.03) significantly increased registrations. A single-paper meta-analysis assessing these studies indicated all 3 appeals resulted in significantly greater registrations than the control (OR ranged from 1.06 to 1.13)., Conclusion: Results indicate donor registration rates can be increased through DMV-based media campaigns; however, the appeal used, and the implementation of that appeal, can determine the likelihood of success. These results can guide the development and implementation of campaigns seeking to influence donor registration and other prosocial behaviors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).