Background: Reducing mental illness stigma in youth is an important societal goal, but much of the existing literature focuses on knowledge enhancement strategies. These alone may not be sufficient to enhance empathy, change fundamental attitudes, or reduce social distance. Objective: To evaluate a youth-initiated, discussion- and empathy-based antistigma school program, called "Let's Erase the Stigma" (LETS), among adolescents from Los Angeles. We hypothesized that participation in such clubs, for a semester, would be associated with better attitudes toward mental illness, reduced social distance against those with mental illness, and enhanced performance of antistigma actions, but not greater knowledge about mental disorder. Method: Participants were involved in LETS clubs for a semester; non-participants, also interested in such involvement, were evaluated prior to club activities. Outcomes in this quasi-experimental, non-randomized trial included (a) quantitative measures of attitudes, social distance, positive antistigma actions, and knowledge, all related to mental illness; and (b) open-ended responses related to stigma awareness, potential antistigma actions, and antistigma rationale. The design did not allow for evaluation of pre-post differences but afforded insight into potential contributions of LETS participation regarding outcomes of interest. Results: LETS participation was associated with statistically significant differences across attitudes, social distance, antistigma actions, and knowledge, with effect sizes ranging from small to large. Conclusions: Although not meeting the standard of a randomized trial, the findings suggest that a youth-directed, discussion- and action-based intervention may provide a novel means of reducing mental illness stigma in adolescents. The preliminary nature of the results mandates experimental investigations.