This meta-analysis found empirical support for the effectiveness of indicated prevention programs for higher education students at risk for subsequent mental health difficulties based on their current subclinical levels of various presenting problems, such as depression, anxiety, or interpersonal difficulties. A systematic literature search identified 79 controlled published and unpublished interventions involving 4,470 college, graduate, or professional students. Programs were effective at post-intervention overall (ES = 0.49, CI [0.43, 0.55]), and for both targeted outcomes (ES = 0.58, CI [0.51, 0.64]) as well as additional nontargeted outcomes assessed in the studies (ES = 0.32, CI [0.25, 0.39]). Interventions compared with a no-intervention or a wait-list control (ES = 0.64, CI [0.57, 0.71], k = 68) demonstrated significantly larger effects overall than did interventions compared with an attention-placebo control (ES = 0.27, CI [0.11, 0.43], k = 11), although both were significant. Among the former group, modality and presenting problem emerged as significant moderators of intervention effectiveness, and among the 43 of these that assessed effectiveness at an average follow-up period of 35 weeks, the positive effects from intervention remained strong (ES = 0.59, CI [0.50, 0.68]). Overall, programs were fairly brief, attracted and retained students, were positively rated by students, and effective when administered by paraprofessionals as well as professionals. Current findings are promising and stimulate recommendations for improving future research, such as expanding the range of outcomes assessed, and clarifying moderators and mediators of intervention impact.