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Background Symptoms of depression, anxiety, and distress are more common in undergraduates compared to age-matched peers. Mental ill health among students is associated with impaired academic achievement, worse occupational preparedness, and lower future occupational performance. Research on mental health promoting and mental ill health preventing interventions has shown promising short-term effects, though the sustainability of intervention benefits deserve closer attention. We aimed to identify, appraise and summarize existing data from randomized control trials (RCTs) reporting on whether the effects of mental health promoting and mental ill health preventing interventions were sustained at least three months post-intervention, and to analyze how the effects vary for different outcomes in relation to follow-up length. Further, we aimed to assess whether the effect sustainability varied by intervention type, study-level determinants and of participant characteristics. Material and Methods A systematic search in MEDLINE, PsycInfo, ERIC, and Scopus was performed for RCTs published in 1995–2015 reporting an assessment of mental ill health and positive mental health outcomes for, at least, three months of post-intervention follow-up. Random-effect modeling was utilized for quantitative synthesis of the existing evidence with standardized mean difference (Hedges’ g) used to estimate an aggregated effect size. Sustainability of the effects of interventions was analyzed separately for 3–6 months, 7–12 months, and 13–18 months of post-intervention follow-up. Results About 26 studies were eligible after reviewing 6,571 citations. The pooled effects were mainly small, but significant for several categories of outcomes. Thus, for the combined mental ill health outcomes, symptom-reduction sustained up to 7–12 months post-intervention (standardized mean difference (Hedges’ g) effect size (ES) = −0.28 (95% CI [−0.49, −0.08])). Further, sustainability of symptom-reductions were evident for depression with intervention effect lasting up to 13–18 months (ES = −0.30 (95% CI [−0.51, −0.08])), for anxiety up to 7–12 months (ES = −0.27 (95% CI [−0.54, −0.01])), and for stress up to 3–6 months (ES = −0.30 (95% CI [−0.58, −0.03])). The effects of interventions to enhance positive mental health were sustained up to 3–6 months for the combined positive mental health outcomes (ES = 0.32 (95% CI [0.05, 0.59])). For enhanced active coping, sustainability up to 3–6 months was observed with a medium and significant effect (ES = 0.75 (95% CI [0.19, 1.30])). Discussion The evidence suggests long-term effect sustainability for mental ill health preventive interventions, especially for interventions to reduce the symptoms of depression and symptoms of anxiety. Interventions to promote positive mental health offer promising, but shorter-lasting effects. Future research should focus on mental health organizational interventions to examine their potential for students in tertiary education.