Aim: Gatekeeper interventions are universal programs designed for use by the general public that provide brief training sessions in responding to suicidal risk. To date, the evidence base for the efficacy of gatekeeper intervention training programs has been mixed. However, little attention has been paid to potential psychological moderators of the efficacy of suicide gatekeeper interventions. We explore the potential moderating effects of suicide-related stigma and social responsibility on the efficacy of a suicide prevention gatekeeper training program. Methods: Participants were 179 college students with a mean age of 19.05 years (SD = 1.82, range 18–31). Participants were 71.5% women, 48.6% Hispanic, and 19.6% non-Hispanic White. Results: Results indicated that higher scores on suicide-related stigma were associated with smaller intervention effects on gatekeeper self-efficacy. In contrast, higher scores on social responsibility were associated with greater intervention effects with regard to gatekeeper preparedness and gatekeeper likelihood. Conclusion: An improved understanding of the factors associated with efficacy of gatekeeper intervention programs may lead to the development of improved gatekeeper interventions. These findings may also contribute to the development of targeted gatekeeper interventions for specific cultural or occupational groups.