Objective The current study examined the efficacy of an early intervention based on acceptance and commitment therapy (ACT) for depressive symptomatology. The ACT intervention is aimed at increasing the acceptance of negative thoughts and emotions and living a mindful and value-based life. Method Adults with mild to moderate depressive symptomatology were randomly assigned to the ACT intervention (n = 49) or to a waiting list (n = 44). The mean age of the participants was 49 years. The majority of the participants was female and of Dutch origin. All the participants completed measures before and after the intervention, as well as three months later at follow-up to assess depression (CES-D), anxiety (HADS-A), fatigue (CIS), alcohol use and acceptance (AAQ-II). Results The ACT intervention led to statistically significant reduction in depressive symptomatology (Cohen’s d = .60). These reductions were maintained at the three-month follow-up. Also significant reductions in anxiety and fatigue were observed. Moreover, mediational analysis showed that the improvement of acceptance during the intervention mediated the effects of the intervention on depressive symptomatology at follow-up. Conclusion These findings suggest that an early intervention based on ACT, aimed at increasing acceptance, is effective in reducing depressive symptomatology.